靶向抑制NOTCH信号通路诱导胃癌细胞凋亡的网络调控研究
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摘要
目的
NOTCH信号通路在保持细胞增殖、分化和凋亡的平衡等方面都发挥非常重要的作用,目前有大量的研究和临床证据表明NOTCH在许多肿瘤中起原癌基因或者抑癌基因的作用,因此NOTCH通路是肿瘤治疗的一个潜在靶点。我们前期研究发现NOTCH信号通路在胃癌中存在异常表达,本研究探讨靶向抑制NOTCH信号通路应用于胃癌治疗的可能性,同时阐释抑制该信号通路诱导胃癌细胞凋亡的机制,为胃癌的治疗提供新思路和科学依据。
方法
将胃癌重要致癌因子(幽门螺杆菌)H. pylori和正常胃粘膜细胞株共培养24h后,通过RT2Profiler PCR Array-Human Signal Transduction Pathway Finder基因芯片筛选H. pylori感染后出现异常表达的信号通路。将不同H. pylori菌株与胃粘膜细胞共培养后,利用荧光定量PCR和Western Blot验证上一步筛选出的通路。使用NOTCH信号通路抑制剂GSI和受体配体siRNA处理三种胃癌细胞株MKN-45、SGC-7901、BGC-823,利用流式细胞仪Annexin-V-FITC/PI双染法检测抑制Notch信号通路对胃癌细胞周期及凋亡的影响,通过RT2Profiler PCR Array-Human Signal Transduction Pathway Finder基因芯片分析胃癌细胞中NOTCH信号通路与其它信号通路的cross-talking,通过Human Apoptosis Antibody Array抗体芯片阐释阻断NOTCH信号通路诱导胃癌细胞凋亡的机制。
结果
正常胃粘膜细胞株与H. pylori11637共培养后,通过RT2Profiler PCR Array-Human Signal Transduction Pathway Finder基因芯片检测有22个基因表达水平具有差异,这些基因主要与细胞增殖、细胞周期和转录调控相关,DAVID Pathway分析显示H. pylori感染后主要影响了Cyclins and Cell Cycle Regulation和NOTCH Signaling Pathway这两条通路。PCR及Western Blot结果验证了H. pylori不同菌株11637和SS1感染胃粘膜细胞后,NOTCH配体DLL4表达水平显著上升。流式细胞仪检测证实两种菌株通过调控细胞周期相关蛋白,抑制了细胞增殖。
使用20μmol/L GSI (S2188)作用于胃癌细胞株BGC-823、MKN-45、 SGC-790124h后受体NOTCH1、NOTCH2和靶基因HES1的mRNA和相应蛋白表达水平都显著受到了抑制；抑制剂使得胃癌细胞停滞于G1期,阻止细胞DNA合成进而影响其有丝分裂,抑制了细胞的增殖,并且诱导胃癌细胞发生凋亡。NOTCH2siRNA和DLL4siRNA均能显著抑制相应蛋白表达水平,通路靶基因HES1表达水平显著下降,siRNA组胃癌细胞周期无明显变化,但与GSI组相同显著诱导了胃癌细胞的凋亡。采用Array-Human Signal Transduction PathwayFinder分别对GSI、NOTCH2siRNA和DLL4siRNA处理后的胃癌细胞MKN-45进行基因表达分析发现,三组无显著差异,NOTCH信号通路与WNT信号通路、P53信号通路和缺氧信号通路密切相关。Human Apoptosis Antibody Array抗体芯片分别对GSI、NOTCH2siRNA和DLL4siRNA处理后的MKN-45进行蛋白差异表达分析发现,GSI组差异蛋白既含有死亡受体途径的蛋白,同时线粒体凋亡途径中的多个蛋白也上调；siRNA组只有肿瘤坏死因子受体蛋白上调,说明两种抑制方法通过不同机制调控胃癌细胞的凋亡。
结论
NOTCH信号通路可做为胃癌治疗的潜在靶点,靶向抑制NOTCH受体或配体与抑制剂效果相似,其通过调控WNT信号通路、P53信号通路和缺氧信号通路相互作用,使胃癌细胞增殖降低并诱导发生凋亡,其凋亡机制有所差异：配体或受体siRNA通过死亡受体途径,抑制剂GSI通过死亡受体途径和线粒体途径两种方式诱导凋亡。
Aims
NOTCH signaling plays an important role in cell proliferation, differentiation and apoptosis. A growing body of research and clinical evidence are in support of NOTCH's oncogenic or tumor suppressive role in a wide variety of cancers. It, therefore, places Notch signaling as a potential target for cancer therapeutics. Our previous study found that abnormal expression of the NOTCH signaling pathway in gastric cancer. The aim of this study was to investigate the possibility of NOTCH signaling pathway as a potential therapeutic target in gastric cancer, and explain the molecular mechanism which inhibition of Notch pathway induces apoptosis in gastric cancer cells. It would provide a theoretical basis for the treatment of gastric cancer.
Methods
Gastric epithelial cell line GES-1was co-cultured with H. pylori for24h. The signaling pathways activated by H. pylori were identified by RT2Profiler PCR Array-Human Signal Transduction Pathway Finder microarray. Total RNA and protein were isolated from GES-1incubation with different strains of H. pylori and were cocultured for24h. The activated signaling pathway verified by qPCR and Western Blot. Gastric cancer lines (MKN-45, SGC-7901, BGC-823) will be treated with or without GSI, Notch receptor siRNA and ligands siRNA. Cell cycle and apoptosis were detected by Annexin-V-FITC/PI and flow cytometry. Cross-talking between NOTCH signaling pathway and other signaling pathways analyzed by RT2Profiler PCR Array-Human Signal Transduction Pathway Finder microarray. The molecular mechanism which inhibition of NOTCH pathway induces apoptosis in gastric cancer cells analyzed by Human Apoptosis Antibody Array.
Results
There are22different expression genes between GSI with and without H. pylori11637by RT2Profiler PCR Array-Human Signal Transduction Pathway Finder microarray. These genes were associated with cell proliferation, cell cycle and transcriptional regulation. DAVID Pathway analysis showed that the H. pylori infection mainly affects Cyclins and Cell Cycle Regulation and NOTCH Signaling Pathway. The expression levels of NOTCH ligand DLL4were significantly increased by H. pylori11637and SSI. H. pylori inhibited cell proliferation through the regulation of cell cycle-related proteins.
Gastric cancer cell lines (BGC-823, MKN-45, SGC-7901) were treated with or without20μmol/L GSI for24h. The expression levels of mRNA and protein of NOTCH1, NOTCH2and HES1were inhibited significantly. Inhibitor induced cell-cycle arrest in G1phase, inhibited cell proliferation and induced apoptosis. NOTCH2siRNA and DLL4siRNA significantly inhibited the expression of the corresponding protein levels and decreased significantly HES1. siRNA group did not affect gastric cancer cell cycle. Both GSI group and siRNA group induced significantly gastric cancer cells apoptosis. NOTCH signaling pathway closely related to WNT signaling pathway, P53signaling pathway and hypoxia signaling pathways by analysis of Array-Human Signal Transduction Pathway Finder in group GSI, NOTCH2siRNA and DLL4siRNA treatment gastric cancer cell MKN-45. Human Apoptosis Antibody Array was used to identify differentially expressed protein related apoptosis in the control and GSI, NOTCH2siRNA and DLL4siRNA treatment. Our results showed that a number of apoptotic signaling proteins were modulated following treatment. Some proteins related mitochondrial pathway were elevated in GSI group. Tumor necrosis factor-a and its receptors were significantly higher in all treatment group as compared with control.
Conclusion
NOTCH signaling can be used as a potential target for the treatment of gastric cancer. There are similar effect in inhibitors, NOTCH receptor siRNA and ligand siRNA. Inhibition of NOTCH signaling pathway could reduce gastric cancer cell proliferation and induce apoptosis, through regulating WNT signaling pathway, P53signaling pathway, and hypoxia signaling pathways. siRNA induced cell apoptosis via death receptor-mediated pathway. GSI induced cell apoptosis via both the mitochondrial and death receptor-mediated pathway.
NOTCH信号通路在保持细胞增殖、分化和凋亡的平衡等方面都发挥非常重要的作用,目前有大量的研究和临床证据表明NOTCH在许多肿瘤中起原癌基因或者抑癌基因的作用,因此NOTCH通路是肿瘤治疗的一个潜在靶点。我们前期研究发现NOTCH信号通路在胃癌中存在异常表达,本研究探讨靶向抑制NOTCH信号通路应用于胃癌治疗的可能性,同时阐释抑制该信号通路诱导胃癌细胞凋亡的机制,为胃癌的治疗提供新思路和科学依据。
方法
将胃癌重要致癌因子(幽门螺杆菌)H. pylori和正常胃粘膜细胞株共培养24h后,通过RT2Profiler PCR Array-Human Signal Transduction Pathway Finder基因芯片筛选H. pylori感染后出现异常表达的信号通路。将不同H. pylori菌株与胃粘膜细胞共培养后,利用荧光定量PCR和Western Blot验证上一步筛选出的通路。使用NOTCH信号通路抑制剂GSI和受体配体siRNA处理三种胃癌细胞株MKN-45、SGC-7901、BGC-823,利用流式细胞仪Annexin-V-FITC/PI双染法检测抑制Notch信号通路对胃癌细胞周期及凋亡的影响,通过RT2Profiler PCR Array-Human Signal Transduction Pathway Finder基因芯片分析胃癌细胞中NOTCH信号通路与其它信号通路的cross-talking,通过Human Apoptosis Antibody Array抗体芯片阐释阻断NOTCH信号通路诱导胃癌细胞凋亡的机制。
结果
正常胃粘膜细胞株与H. pylori11637共培养后,通过RT2Profiler PCR Array-Human Signal Transduction Pathway Finder基因芯片检测有22个基因表达水平具有差异,这些基因主要与细胞增殖、细胞周期和转录调控相关,DAVID Pathway分析显示H. pylori感染后主要影响了Cyclins and Cell Cycle Regulation和NOTCH Signaling Pathway这两条通路。PCR及Western Blot结果验证了H. pylori不同菌株11637和SS1感染胃粘膜细胞后,NOTCH配体DLL4表达水平显著上升。流式细胞仪检测证实两种菌株通过调控细胞周期相关蛋白,抑制了细胞增殖。
使用20μmol/L GSI (S2188)作用于胃癌细胞株BGC-823、MKN-45、 SGC-790124h后受体NOTCH1、NOTCH2和靶基因HES1的mRNA和相应蛋白表达水平都显著受到了抑制；抑制剂使得胃癌细胞停滞于G1期,阻止细胞DNA合成进而影响其有丝分裂,抑制了细胞的增殖,并且诱导胃癌细胞发生凋亡。NOTCH2siRNA和DLL4siRNA均能显著抑制相应蛋白表达水平,通路靶基因HES1表达水平显著下降,siRNA组胃癌细胞周期无明显变化,但与GSI组相同显著诱导了胃癌细胞的凋亡。采用Array-Human Signal Transduction PathwayFinder分别对GSI、NOTCH2siRNA和DLL4siRNA处理后的胃癌细胞MKN-45进行基因表达分析发现,三组无显著差异,NOTCH信号通路与WNT信号通路、P53信号通路和缺氧信号通路密切相关。Human Apoptosis Antibody Array抗体芯片分别对GSI、NOTCH2siRNA和DLL4siRNA处理后的MKN-45进行蛋白差异表达分析发现,GSI组差异蛋白既含有死亡受体途径的蛋白,同时线粒体凋亡途径中的多个蛋白也上调；siRNA组只有肿瘤坏死因子受体蛋白上调,说明两种抑制方法通过不同机制调控胃癌细胞的凋亡。
结论
NOTCH信号通路可做为胃癌治疗的潜在靶点,靶向抑制NOTCH受体或配体与抑制剂效果相似,其通过调控WNT信号通路、P53信号通路和缺氧信号通路相互作用,使胃癌细胞增殖降低并诱导发生凋亡,其凋亡机制有所差异：配体或受体siRNA通过死亡受体途径,抑制剂GSI通过死亡受体途径和线粒体途径两种方式诱导凋亡。
Aims
NOTCH signaling plays an important role in cell proliferation, differentiation and apoptosis. A growing body of research and clinical evidence are in support of NOTCH's oncogenic or tumor suppressive role in a wide variety of cancers. It, therefore, places Notch signaling as a potential target for cancer therapeutics. Our previous study found that abnormal expression of the NOTCH signaling pathway in gastric cancer. The aim of this study was to investigate the possibility of NOTCH signaling pathway as a potential therapeutic target in gastric cancer, and explain the molecular mechanism which inhibition of Notch pathway induces apoptosis in gastric cancer cells. It would provide a theoretical basis for the treatment of gastric cancer.
Methods
Gastric epithelial cell line GES-1was co-cultured with H. pylori for24h. The signaling pathways activated by H. pylori were identified by RT2Profiler PCR Array-Human Signal Transduction Pathway Finder microarray. Total RNA and protein were isolated from GES-1incubation with different strains of H. pylori and were cocultured for24h. The activated signaling pathway verified by qPCR and Western Blot. Gastric cancer lines (MKN-45, SGC-7901, BGC-823) will be treated with or without GSI, Notch receptor siRNA and ligands siRNA. Cell cycle and apoptosis were detected by Annexin-V-FITC/PI and flow cytometry. Cross-talking between NOTCH signaling pathway and other signaling pathways analyzed by RT2Profiler PCR Array-Human Signal Transduction Pathway Finder microarray. The molecular mechanism which inhibition of NOTCH pathway induces apoptosis in gastric cancer cells analyzed by Human Apoptosis Antibody Array.
Results
There are22different expression genes between GSI with and without H. pylori11637by RT2Profiler PCR Array-Human Signal Transduction Pathway Finder microarray. These genes were associated with cell proliferation, cell cycle and transcriptional regulation. DAVID Pathway analysis showed that the H. pylori infection mainly affects Cyclins and Cell Cycle Regulation and NOTCH Signaling Pathway. The expression levels of NOTCH ligand DLL4were significantly increased by H. pylori11637and SSI. H. pylori inhibited cell proliferation through the regulation of cell cycle-related proteins.
Gastric cancer cell lines (BGC-823, MKN-45, SGC-7901) were treated with or without20μmol/L GSI for24h. The expression levels of mRNA and protein of NOTCH1, NOTCH2and HES1were inhibited significantly. Inhibitor induced cell-cycle arrest in G1phase, inhibited cell proliferation and induced apoptosis. NOTCH2siRNA and DLL4siRNA significantly inhibited the expression of the corresponding protein levels and decreased significantly HES1. siRNA group did not affect gastric cancer cell cycle. Both GSI group and siRNA group induced significantly gastric cancer cells apoptosis. NOTCH signaling pathway closely related to WNT signaling pathway, P53signaling pathway and hypoxia signaling pathways by analysis of Array-Human Signal Transduction Pathway Finder in group GSI, NOTCH2siRNA and DLL4siRNA treatment gastric cancer cell MKN-45. Human Apoptosis Antibody Array was used to identify differentially expressed protein related apoptosis in the control and GSI, NOTCH2siRNA and DLL4siRNA treatment. Our results showed that a number of apoptotic signaling proteins were modulated following treatment. Some proteins related mitochondrial pathway were elevated in GSI group. Tumor necrosis factor-a and its receptors were significantly higher in all treatment group as compared with control.
Conclusion
NOTCH signaling can be used as a potential target for the treatment of gastric cancer. There are similar effect in inhibitors, NOTCH receptor siRNA and ligand siRNA. Inhibition of NOTCH signaling pathway could reduce gastric cancer cell proliferation and induce apoptosis, through regulating WNT signaling pathway, P53signaling pathway, and hypoxia signaling pathways. siRNA induced cell apoptosis via death receptor-mediated pathway. GSI induced cell apoptosis via both the mitochondrial and death receptor-mediated pathway.
引文
Adler, S.H., Chiffoleau, E., Xu, L., Dalton, N.M., Burg, J.M., Wells, A.D., et al. (2003). Notch signaling augments T cell responsiveness by enhancing CD25 expression. Journal of Immunology,171,2896-2903.
Amsen, D., Blander, J.M., Lee, G.R., Tanigaki, K., Honjo, T., Flavell, R.A. (2004). Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell,117,515-526.
Barten, D. M., Meredith, J. E., Jr., Zaczek, R., Houston, J. G.,& Albright, C. F. (2006). Gamma-secretase inhibitors for Alzheimer's disease:balancing efficacy and toxicity. Drugs in Rerearch and Development,7,87-97.
Beel, A.J., Sanders, C.R. (2008). Substrate specificity of gamma-secretase and other intramembrane proteases. Cellular and Molecular Life Science,65,1311-1334.
Beverly, L.J., Felsher, D.W., Capobianco, A.J. (2005). Suppression of p53 by Notch in lymphomagenesis:implications for initiation and regression. Cancer Resesrch,65,7159-7168.
Borghese, L., Dolezalova, D., Opitz, T., Haupt, S., Leinhaas, A., Steinfarz, B., et al. (2010). Inhibition of Notch Signaling in Human Embryonic Stem Cell-Derived Neural Stem Cells Delays Gl/S Phase Transition and Accelerates Neuronal Differentiation In Vitro and In Vivo. Stem Cells,28,955-964.
Borriello, A., Pietra, V.D., Criscuolo, M., Oliva, A., Tonini, G.P., Iolascon, A., et al. (2000). p27(Kipl) accumulation is associated with retinoic-induced neuroblastoma differentiation: evidence of a decreased proteasome-dependent degradation. Oncogene,19,51-60.
Caruso, R., Fina, D., Peluso, I., Fantini, M.C., Tosti, C., Del Vecchio, B.G., et al. (2007). IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. Journal of Immunology,178,5957-5965.
Chen, X., Zhang, T., Shi, J., Xu, P., Gu, Z., Sandham, A. et al. (2013) Notch1 Signaling Regulates the Proliferation and Self-Renewal of Human Dental Follicle Cells by Modulating the G1/S Phase Transition and Telomerase Activity. PLoS ONE 8(7):e69967. doi:10.1371/journal.pone.0069967
Cho, O.H., Shin, H.M., Miele, L., Golde, T.E., Fauq, A., Minter, L.M., et al. (2009). Notch regulates cytolytic effector function in CD8+ T cells. Journal of Immunology,182,3380-3389.
de Martel, C., Ferlay, J., Franceschi, S., Vignat, J., Bray, F., Forman, D., et al. (2012). Global burden of cancers attributable to infections in 2008:a review and synthetic analysis. Lancet Oncology,13,607-615.
Dirlam, A., Spike, B.T., MacLeod, K.F. (2007). Deregulated E2f-2 underlies cell cycle and maturation defects in retino-blastoma null erythroblasts. Molecular and Cellular Biology,27, 8713-8728.
Ferrand, J., Lehours, P., Schmid-Alliana, A., Megraud, F., Varon, C. (2011). Helicobacter pylori infection of gastrointestinal epithelial cells in vitro induces mesenchymal stem cell migration through an NF-kappaB-dependent pathway. PLoS ONE,6, e29007.
Foo, J.H., Culvenor, J.G., Ferrero, R.L., Kwok, T., Lithgow, T., Gabriel, K. (2010). Both the p33 and p55 subunits of the Helicobacter pylori VacA toxin are targeted to mammalian mitochondria. Journal of Molecular Biology,401,792-798.
Fre, S., Pallavi, S. K., Huyghe, M., Lae, M., Janssen, K.P., Robine, S. et al. (2009). Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proceedings of the National Academy of Sciences of the United States of America,106,6309-6314.
Galmiche, A., Rassow, J. (2010). Targeting of Helicobacter pylori VacA to mitochondria. Gut Microbes,1,392-395.
Gujuluva, C.N., Baek, J.H., Shin, K.H., Cherrick, H.M., Park, N.H. (1994). Effect of UV-irradiation on cell cycle, viability and the expression of p53, gaddl53 and gadd45 genes in normal and HPV-immortalized human oral keratinocytes. Oncogene,9,1819-1827.
Guo, W., Lasky, J.L., Chang, C.J., Mosessian, S., Lewis, X., Xiao, Y., et al. (2008). Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation. Nature 453,529-533.
Hemming, M.L, Elias, J.E., Gygi, S.P., Selkoe, D.J. (2008). Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biology,6, e257.
Herrera, V., Parsonnet, J. (2009). Helicobacter pylori and gastric adenocarcinoma. Clinical Microbiology and Infection,15,971-976.
Hiyama, A., Skubutyte, R., Markova, D., Anderson, D.G., Yadla, S., Sakai, D., et al. (2011). Hypoxia activates the notch signaling pathway in cells of the intervertebral disc:implications in degenerative disc disease. Arthritis & Rheumatology,63,1355-1364.
Ito, T., Schaller, M., Hogaboam, C.M., Standiford, T.J., Sandor, M., Lukacs, N.W., et al. (2009). TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4. Journal of Clinical Investigation,119, 33-46.
Jin, S., Tong, T., Fan, W., Fan, F., Antinore, M.J., Zhu, X., et al. (2002). GADD45-induced cell cycle G2-M arrest associates with altered subcellular distribution of cyclin B1 and is independent of p38 kinase activity. Oncogene,21,8696-8704.
Joshi, I., Minter, L.M., Telfer, J., Demarest, R.M., Capobianco, A.J., Aster, J.C., et al. (2009). Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood,113,1689-1698.
Kastan, M.B., Zhan, Q., el-Deiry, W.S., Carrier, F., Jacks, T., Walsh, W.V., et al. (1992). A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell,71,587-597.
Kim, T.H., Shivdasani, R.A. (2011). Notch signaling in stomach epithelial stem cell homeostasis. Journal of Experimental Medicine,208,677-688.
Kimura, K., Satoh, K., Kanno, A., Hamada, S., Hirota, M., Endoh, M., et al. (2007). Activation of Notch signaling in tumorigenesis of experimental pancreatic cancer induced by dimethylbenzanthracene in mice. Cancer Science,98,155-162.
LaVoie, M. J., Selkoe, D. J. The Notch ligands, Jagged and Delta, are sequentially processed by a-secretase and presenilin/y-secretase and release signaling fragments. Journal of Biological Chemistry,278,34427-34437 (2003).
Lee, I.O., Kim, J.H., Choi, Y.J., Pillinger, M.H., Kim, S.Y., Blaser, M.J., et al. (2010). Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. Journal of Biological Chemistry,285,16042-16050.
Lleo, A. (2008). Activity of gamma-secretase on substrates other than APP. Current Topics in Medicinal Chemistry,8,9-16.
Maekawa, Y., Minato, Y., Ishifune, C., Kurihara, T., Kitamura, A., Kojima, H., et al. (2008). Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nature Immunology,9,1140-1147.
Mukherjee, S., Schaller, M.A., Neupane, R., Kunkel, S.L., Lukacs, N.W. (2009). Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. Journal of Immunology,182,7381-7388.
Mungamuri, S.K., Yang, X., Thor, A.D., Somasundaram, K. (2006). Survival signaling by Notch 1:mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Resesrch, 66,4715-4724.
Nagy, T.A., Frey, M.R., Yan, F., Israel, D.A., Polk, D.B., Peek, Jr R.M. (2009). Helicobacter pylori Regulates Cellular Migration and Apoptosis by Activation of Phosphatidylinositol 3-Kinase Signaling. Journal Of Infectious Diseases,199,641-651.
Nair, P., Somasundaram, K., Krishna, S. (2003). Activated Notch1 inhibits p53-induced apoptosis and sustains transformation by human papillomavirus type 16 E6 and E7 oncogenes through a PI3K-PKB/Aktdependent pathway. Journal of Virology,77,7106-7112.
Noseda, M., Chang, L., McLean, G., Grim, J.E., Clurman, B.E., Smith, L.L., et al. (2004). Notch Activation Induces Endothelial Cell Cycle Arrest and Participates in Contact Inhibition: Role of p21Cip1 Repression. Molecular and Cellular Biology,24,8813-8822.
O'Neil, J., Grim, J., Strack, P., Rao, S., Tibbitts, D., Winter, C., et al. (2007). FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. Journal of Experimental Medicine,204,1813-1824.
Palaga, T., Miele, L., Golde, T.E., Osborne, B.A. (2003). TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells. Journal of Immunology, 171,3019-3024.
Palomero, T., Sulis, M. L., Cortina, M., Real, P. J., Barnes, K., Ciofani, M., et al. (2007). Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nature Medicine,13,1203-1210.
Palomero, T., Dominguez, M., Ferrando, A.A. (2008). The role of the PTEN/AKT pathway in NOTCH1-induced leukemia. Cell Cycle,7,965-970
Polk, D.B.,& Peek, R.M. Jr. (2010). Helicobacter pylori:gastric cancer and beyond. Nature Reviews Cancer,10,403-414.
Radtke, F., Fasnacht, N., MacDonald H. R. (2010). Notch Signaling in the Immune System. Immunity,32,14-27.
Rao, S.S., O'Neil, J., Liberator, C.D., Hardwick, J.S., Dai, X., Zhang, T., et al. (2009). Inhibition of NOTCH Signaling by Gamma Secretase Inhibitor Engages the RB Pathway and Elicits Cell Cycle Exit in T-Cell Acute Lymphoblastic Leukemia Cells. Cancer Resesrch,69, 3060-3068.
Ricci, V., Romano, M., Boquet, P., (2011). Molecular cross-talk between Helicobacter pylori and human gastric mucosa. World Journal of Gastroenterology,17,1383-1399.
Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature, 447,330-333.
Sahlgren, C., Gustafsson, M.V., Jin, S., Poellinger, L., Lendahl U. (2008). Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proceedings of the National Academy of Sciences of the United States of America,105,6392-6397.
Six, E., Ndiaye, D., Laabi, Y., et al. The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and y-secretase. Proceedings of the National Academy of Sciences of the United States of America,100,7638-7643 (2003).
Shi, Y., Liu, X.F., Zhuang, Y., Zhang, J,Y, Liu, T., Yin, Z.N., et al. (2010). Helicobacter pylori-Induced Th17 Responses Modulate Thl Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice. Journal of Immunology,184,5121-5129.
Smith, S.M., Moran, A.P., Duggan, S.P., Ahmed, S.E., Mohamed, A.S., Windle, H.J., et al. (2011). Tribbles 3:a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide. Journal of Immunology,186,2462-2471.
Skokos, D.,& Nussenzweig, M.C. (2007). CD8-DCs induce IL-12-independent Thl differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. Journal of Experimental Medicine,204,1525-1531.
Sun, J., Krawczyk, C.J., Pearce, E.J. (2008). Suppression of Th2 cell development by Notch ligands Deltal and Delta4. Journal of Immunology,180,1655-1661.
Sun, H.W., Wu, C.,,Tan H.Y., Wang,Q.S. (2012). Combination DLL4 with Jagged 1-siRNA can Enhance Inhibition of the Proliferation and Invasiveness Activity of Human Gastric Carcinoma by Notchl/VEGF Pathway. Hepato-Gastroenterology,59,924-929.
Tegtmeyer, N., Hartig, R., Delahay, R.M., Rohde, M., Brandt, S., Conradi, J., et al. (2010). A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation. Journal of Biological Inorganic Chemistry,285,23515-23526.
Tegtmeyer, N., Wessler, S., Backert, S. (2011a). Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. The Federation of European Biochemical Societies Journal,278,1190-1202.
Tegtmeyer, N., Wittelsberger, R., Hartig, R., Wessler, S., Martinez-Quiles, N., Backert, S. (2011b). Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori. Cell Host Microbe,9,520-531.
Tsang, Y.H., Lamb, A., Romero-Gallo, J., Huang, B., Ito, K., Peek, Jr R.M., et al. (2010). Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene,29,5643-5650.
Uren, A.G., Kool, J., Matentzoglu, K., de Ridder, J., Mattison, J., van Uitert, M., et al. (2008). Large-scale mutagenesis in p19(ARF)-and p53-deficient mice identifies cancer genes and their collaborative networks. Cell,133,727-741.
Wang, H., Sun,Y., Liu, S., Yu, H., Li, W., Zeng, J., et al. (2011). Upregulation of progranulin by Helicobacter pylori in humangastric epithelial cellsvia p38MAPK and MEK1/2 signaling pathway:role in epithelial cell proliferationand migration. FEMS Immunology and Medical Microbiology,63,82-92.
Wang, Z., Li, Y., Ahmad, A., Banerjee, S., Azmi, A.S., Kong, D., et al. (2011). Down-regulation of Notch-1 is associated with Akt and FoxMl in inducing cell growth inhibition and apoptosis in prostate cancer cells. Journal of Cellular Biochemistry,112,78-88.
Wang, Z., Parikh, H., Jia, J., Myers, T., Yeager, M., Jacobs, K.B.,et al. (2012). Helicobacter pylori CagA inhibits the expression of Runx3 via Src/MEK/ERK and p38 MAPK pathways in gastric epithelial cell. Journal of Cellular Biochemistry,113,1080-1086.
Watanabe, T., Asano, N., Fichtner-Feigl, S., Gorelick, P.L., Tsuji, Y., Matsumoto, Y., et al. (2010). NODI contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the 1SGF3 signaling pathway. Journal of Clinical Investigation,120, 1645-1662.
Wong, G.T., Manfra, D., Poulet, F.M., Zhang, Q., Josien, H., Bara, T., et al. (2004). Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits betaamyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. Journal of Biological Chemistry,279, 12876-12882.
Yao, J., Qian, C., Shu, T., Zhang, X., Zhao, Z., Liang, Y. (2013). Combination treatment of PD98059 and DAPT in gastric cancer through induction of apoptosis and downregulation of WNT/β-catenin. Cancer Biology & Therapy,14,833-839.
Abcam. DAPT. http://www.abcam.com/DAPT-ab120633.html (29 April 2013, date last accessed).
Amsen, D., Antov, A., Jankovic, D., Sher, A., Radtke, F., Souabni, A., et al. (2007). Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity,27,89-99.
Arora, P. S.& Ansari, A. Z. (2009). Chemical biology:a Notch above other inhibitors. Nature, 462,171-173.
Backert, S.& Naumann, M. (2010). What a disorder:proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiology,18,479-486.
Backert, S., Tegtmeyer, N., Selbach, M. (2010). The versatility of Helicobacter pylori CagA effector protein functions:the master key hypothesis. Helicobacter,15,163-176.
Barry, D.P., Asim, M., Leiman, D.A., de Sablet, T., Singh, K., Casero, R.A., et al. (2011). Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction. PLoS ONE,28, e17510.
Barten, D. M., Meredith, J. E., Jr., Zaczek, R., Houston, J. G., Albright, C. F. (2006). Gamma-secretase inhibitors for Alzheimer's disease:balancing efficacy and toxicity. Drugs in Rerearch and Development,7,87-97.
Bedogni, B., Warneke, J. A., Nickoloff, B. J., Giaccia, A. J., Powell, M. B. (2008). Notchl is an effector of Akt and hypoxia in melanoma development. Journal of Clinical Investigation,118, 3660-3670.
Beel, A.J.& Sanders, C.R. (2008). Substrate specificity of gamma-secretase and other intramembrane proteases. Cellular and Molecular Life Science,65,1311-1334.
Bozkulak, E. C.& Weinmaster, G. (2009). Selective use of ADAM10 and ADAM17 in activation of Notchl signaling. Molecular and Cellular Biology,29,5679-5695.
Brou, C., Logeat, F., Gupta, N., Bessia, C., LeBail, O., Doedens, J. R., et al. (2000). A novel proteolytic cleavage involved in Notch signaling:the role of the disintegrin-metalloprotease TACE. Molecular Cell,5,207-216.
Cavallo, P., Cianciulli, A., Mitolo, V., Panaro, M.A. (2010). Lipopolysaccharide (LPS) of Helicobacter modulates cellular DNA repair systems in intestinal cells. Clinical and Experimental Medicine,11(3),171-179.
Chang, P.C., Wang, C.J., You, C.K., Kao, M.C. (2011). Effects of a HP0859 (rfaD) knockout mutation on lipopolysaccharide structure of Helicobacter pylori 26695 and the bacterial adhesion on AGS cells. Biochemical and Biophysical Research Communications,405,497-502.
Cheng, P., Zlobin, A., Volgina, V., Gottipati, S., Osborne, B., Simel, E. J., et al. (2001). Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. Journal of Immunology, 167,4458-4467.
Children's Oncology Group. (2012) Gamma-secretase inhibitor RO4929097 in treating young patients with relapsed or refractory solid tumors, CNS tumors, lymphoma, or T-cell leukemia (NCT01088763).
Cohen, B., Shimizu, M., Izrailit, J., Ng, N. F., Buchman, Y., Pan, J. G., et al. (2009). Cyclin D1 is a direct target of JAG 1-mediated Notch signaling in breast cancer. Breast Cancer Research and Treatment,123,113-124.
De Koning, L., Corpet, A., Haber, J. E., Almouzni, G. (2007). Histone chaperones:an escort network regulating histone traffic. Nature Structural & Molecular Biology,14,997-1007.
De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., et al. (1999). A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature,398,518-522.
Delwig, A.& Rand, M. D. (2008). Kuz and TACE can activate Notch independent of ligand. Cellular and Molecular Life Science,65,2232-2243.
Ding, S.Z., Fischer, W., Kaparakis-Liaskos, M., Liechti, G., Merrell, D.S., Grant, P.A., et al. (2010).Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS ONE,5, e9875.
Espinosa, L., Ingles-Esteve, J., Aguilera, C., Bigas, A. (2003). Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. Journal of Biological Chemistry,278,32227-32235.
Eitoku, M., Sato, L., Senda, T., Horikoshi, M. (2008). Histone chaperones:30 years from isolation to elucidation of the mechanisms of nucleosome assembly and disassembly. Cellular and Molecular Life Science,65,414-444.
Falk, R., Falk, A., Dyson, M.R., Melidoni, A.N., Parthiban, K., Young, J.L. et al. (2012) Generation of anti-Notch antibodies and their application in blocking Notch signalling in neural stem cells. Methods,58,69-78.
Fontana, J. R.& Posakony, J. W. (2009). Both inhibition and activation of Notch signaling rely on a conserved neuralized-binding motif in bearded proteins and the Notch ligand Delta. Developmental Biology,333,373-385.
Foo, J.H., Culvenor, J.G., Ferrero, R.L., Kwok, T., Lithgow, T., Gabriel, K. (2010). Both the p33 and p55 subunits of the Helicobacter pylori VacA toxin are targeted to mammalian mitochondria. Journal of Molecular Biology,401,792-798.
Galmiche, A.& Rassow, J. (2010).Targeting of Helicobacter pylori Vac A to mitochondria. Gut Microbes,1,392-395.
Garzia, L., Andolfo, I., Cusanelli, E., Marino, N., Petrosino, G., De Martino, D., et al. (2009). MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PLoS One,4, e4998.
Ge, R., Sun, X., Xiao, C., Yin, X., Shan, W., Chen, Z., et al. (2011). Phosphoproteome analysis of the pathogenic bacterium Helicobacter pylori reveals over-representation of tyrosine phosphorylation and multiply phosphorylated proteins. Proteomics,11,1449-1461.
Goodfellow, H., Krejci, A., Moshkin, Y., Verrijzer, C. P., Karch, F., Bray, S. J. (2007). Gene-specific targeting of the histone chaperone asfl to mediate silencing. Developmental Cell, 13,593-600.
Grubman, A., Kaparakis, M., Viala, J., Allison, C., Badea, L., Karrar, A., et al. (2010). The innate immune molecule, NOD1, regulates direct killing of Helicobacter pylori by antimicrobial peptides. Cell Microbiology,12,626-639.
Hallahan, A. R., Pritchard, J. I., Hansen, S., Benson, M., Stoeck, J., Hatton, B. A., et al. (2004). The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Research,64,7794-7800.
He, F., Saito, K., Kobayashi, N., Harada, T., Watanabe, S., Kigawa, T., et al. (2009). Structural and functional characterization of the NHR1 domain of the Drosophila neuralized E3 ligase in the notch signaling pathway. Journal of Molecular Biology,393,478-495.
Hemming, M.L, Elias, J.E., Gygi, S.P., Selkoe, D.J. (2008). Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biology,6, e257.
H. Lee Moffitt Cancer Center and Research Institute. (2012) An open-label study of RO4929097 in metastatic colorectal cancer (NCT01116687).
Hoey, T., Yen, W. C., Axelrod, F., Basi, J., Donigian, L., Dylla, S., et al. (2009). DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell,5, 168-177.
Howells,L.M., Sale, S., Sriramareddy, S.N., Irving, G.R., Jones, D.J., Ottley, C.J.,et al. (2011). Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. International Journal of Cancer,129,476-486.
http://clinicaltrials.gov/ct2/show/NCT00106145
http://clinicaltrials.gov/ct2/show/NCT00878189
Hug, I., Couturier, M.R., Rooker, M.M., Taylor, D.E., Stein, M., Feldman, M.F. (2010). Helicobacter pylori lipopolysaccharide is synthesized via a novel pathway with an evolutionary connection to protein N-glycosylation. Plos Pathogens,6, e1000819.
Hutton, M.L., Kaparakis-Liaskos, M., Turner, L., Cardona, A., Kwok, T., Ferrero, R.L. (2010). Helicobacter pylori exploits cholesterol-rich microdomains for induction of NF-kappaB-dependent responses and peptidoglycan delivery in epithelial cells. Infection and Immunity,78,4523-4531.
Izon, D. J., Aster, J. C., He, Y., Weng, A., Karnell, F. G., Patriub, V., et al. (2002). Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch 1. Immunity,16, 231-243.
Jenkins, D.W., Ross, S., Veldman-Jones, M., Foltz, I.N., Clavette, B.C., Manchulenko, K., et al. (2012). MEDI0639:a novel therapeutic antibody targeting D114 modulates endothelial cell function and angiogenesis in vivo. Molecular Cancer Therapeutics,11,1650-1660.
Ji, Q., Hao, X., Zhang, M., Tang, W., Yang, M., Li, L., et al. (2009). MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PloS One,4, e6816.
Jin, Y. H., Kim, H., Oh, M., Ki, H., Kim, K. (2009). Regulation of Notch1/NICD and Hesl expressions by GSK-3alpha/beta. Molecules and Cells,27,15-19.
Jurik, A., Hausser, E., Kutter, S., Pattis, I., Prassl, S., Weiss, E., et al. (2010). The coupling protein Cagbeta and its interaction partner CagZ are required for type IV secretion of the Helicobacter pylori CagA protein. Infection and Immunity,78,5244-5251.
Kallifatidis, G., Labsch, S., Rausch, V., Mattern, J., Gladkich, J., Moldenhauer, G., et al. (2011). Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Molecular Therapy,19,188-195.
Kawahara, T., Kawaguchi-Ihara, N., Okuhashi, Y., Itoh, M., Nara, N., Tohda, S. (2009). Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells. Anticancer Research,29,4629-4632.
Kondratyev, M., Kreso, A., Hallett, R.M., Girgis-Gabardo, A., Barcelon, M.E., Ilieva, D., et al. (2012). Gamma-secretase inhibitors target tumorinitiating cells in a mouse model of ERBB2 breast cancer. Oncogene,31,93-103.
Krop,I., Demuth, T., Guthrie, T., Wen, P.Y., Mason, W.P., Chinnaiyan, P., et al. (2012). Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. Journal of Clinical Oncology,30, 2307-2313.
Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C., et al. (2001). Nrarp is a novel intracellular component of the Notch signaling pathway. Genes & Development, 15,1885-1899.
Lee, I.O., Kim, J.H., Choi, Y.J., Pillinger, M.H., Kim, S.Y., Blaser, M.J., et al. (2010). Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. Journal of Biological Chemistry,285,16042-16050.
Lewis, H. D., Leveridge, M., Strack, P. R., Haldon, C. D., O'Neil, J., Kim, H., et al. (2007). Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling. Chemistry & Biology,14,209-219.
Lleo, A. (2008). Activity of gamma-secretase on substrates other than APP. Current Topics in Medicinal Chemistry,8,9-16.
Lichtenthaler, S. F., Ida, N., Multhaup, G., Masters, C. L., Beyreuther, K. (1997). Mutations in the transmembrane domain of APP altering gamma-secretase specificity. Biochemistry,36, 15396-15403.
Li, K., Li, Y., Wu, W., Gordon, W. R., Chang, D. W., Lu, M., et al. (2008). Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3 Journal of Biological Chemistry,283,8046-8054.
Li, Y., Guessous, F., Zhang, Y., Dipierro, C., Kefas, B., Johnson, E., et al. (2009). icroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Research,69, 7569-7576.
Li,Y. et al. (2012) Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch-1 signaling. The Federation of European Biochemical Societies Journal,279,2247-2259.
Lin, W.C., Tsai, H.F., Kuo, S.H., Wu, M.S., Lin, C.W., Hsu, P.I., et al. (2010).Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Research,70,5740-5748.
Liu,S.K., Bham, S.A., Fokas, E., Beech, J., Im, J., Cho, S., et al. (2011) Delta-like ligand 4-notch blockade and tumor radiation response. Journal of the National Cancer Institute,103, 1778-1798.
Liu, Z. J., Shirakawa, T., Li, Y., Soma, A., Oka, M., Dotto, G. P., et al. (2003). Regulation of Notch 1 and D114 by vascular endothelial growth factor in arterial endothelial cells:implications for modulating arteriogenesis and angiogenesis. Molecular and Cellular Biology,23,14-25.
Luistro, L., He, W., Smith, M., Packman, K., Vilenchik, M., Carvajal, D., et al. (2009). Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Research,69,7672-7680.
Maillard, I., Weng, A. P., Carpenter, A. C., Rodriguez, C. G., Sai, H., Xu, L., et al. (2004). Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood,104, 1696-1702.
Maraver,A., Fernandez-Marcos, P.J., Herranz, D., Canamero, M., Munoz-Martin, M., et al. (2012). Therapeutic effect of y-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK. Cancer Cell,22,222-234.
Marshall, B. J.& Warren, J. R. (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet,1(8390):1311-1315.
Martinez, A. M., Schuettengruber, B., Sakr, S., Janic, A., Gonzalez, C., Cavalli, G. (2009). Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling. Nature Genetics,41,1076-1082.
Masuda, S., Kumano, K., Suzuki, T., Tomita, T., Iwatsubo, T., Natsugari, H., et al. (2009). Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model. Cancer Science,100,2444-2450.
Medlmmune (2010). A phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of MEDI0639 in advanced solid tumors (NCT01577745).
Mizuma,M., Rasheed, Z.A., Yabuuchi, S., Omura, N., Campbell, N.R., de Wilde, R.F., et al. (2012). The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models. Molecular Cancer Therapeutics,11,1999-2009.
Moellering, R.E., Cornejo, M., Davis, T.N., Del Bianco, C., Aster, J.C., Blacklow, S.C., et al. (2009). Direct inhibition of the NOTCH transcription factor complex. Nature,462,182-188.
Moshkin, Y.M., Kan, T.W., Goodfellow, H., Bezstarosti, K., Maeda, R.K., Pilyugin, M., et al. (2009). Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Molecular Cell,35,782-793.
Mumm, J.S., Schroeter, E.H., Saxena, M.T., Griesemer, A., Tian, X., Pan, D.J., et al. (2000). A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Molecular Cell,5,197-206.
Murata-Kamiya, N., Kikuchi, K., Hayashi, T., Higashi, H., Hatakeyama, M. (2010). Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell Host Microbe,7,399-411.
Nagaraj, R.& Banerjee, U. (2009). Regulation of Notch and wingless signalling by phyllopod, a transcriptional target of the EGFR pathway. The EMBO Journal,28,337-346.
Nam, Y., Sliz, P., Song, L., Aster, J.C., Blacklow, S.C. (2006). Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell,124, 973-983.
Necchi, V., Sommi, P., Ricci, V., Solcia, E. (2010). In vivo accumulation of Helicobacter pylori products, NODI, ubiquitinated proteins and proteasome in a novel cytoplasmic structure. PLoS ONE,5,e9716.
Nefedova, Y., Sullivan, D.M., Bolick, S.C., Dalton, W.S., Gabrilovich, D.I. (2008). Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood,111,2220-2229.
NIH. (2012) Gamma secretase inhibitor. http://clinicaltrials.gov/ct2/results?term=gamma+secretase+inhibitor& Search=Search.
NIH. (2013) Notch inhibitor cancer. http://www.clinicaltrials.gov/ct2/results?term=notch+inhibitor+cancer& Search=Search.
Noguera-Troise, I., Daly, C., Papadopoulos, N.J., Coetzee, S., Boland, P., Gale, N.W., et al. (2006). Blockade of D114 inhibits tumour growth by promoting non-productive angiogenesis. Nature,444,1032-1037.
Okajima, T.& Irvine, K. D. (2002). Regulation of notch signaling by o-linked fucose. Cell, 111,893-904.
O'Neil, J., Calvo, J., McKenna, K., Krishnamoorthy, V., Aster, J.C., Bassing, C.H., et al. (2006). Activating Notchl mutations in mouse models of T-ALL. Blood,107,781-785.
O'Neil, J., Grim, J., Strack, P., Rao, S., Tibbitts, D., Winter, C., et al. (2007). FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. Journal of Experimental Medicine,204,1813-1824.
Ono, Y., Gnocchi, V.F., Zammit, P.S., Nagatomi, R. (2009). Presenilin-1 acts via Idl to regulate the function of muscle satellite cells in a gamma-secretase-independent manner. Journal of Cell Science,122,4427-4438.
Olbermann, P., Josenhans, C., Moodley, Y., Uhr, M., Stamer, C., Vauterin, M., et al. (2010). A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLOS Genetics,6, e1001069.
Pelz, C., Steininger, S., Weiss, C., Coscia, F., Vogelmann, R. (2011). A novel inhibitory domain of Helicobacter pylori protein CagA reduces CagA effects on host cell biology. Journal of Biological Chemistry,286,8999-9008.
Radin, J.N., Gonza'lez-Rivera, C., Ivie, S.E., McClain, M.S., Cover, T.L. (2011). Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells. Infection and Immunity,79,2535-2543.
Palomero, T., Dominguez, M., Ferrando, A. A. (2008). The role of the PTEN/AKT pathway in NOTCH 1-induced leukemia. Cell Cycle,7,965-970.
Palomero, T., Sulis, M.L., Cortina, M., Real, P.J., Barnes, K., Ciofani, M., et al. (2007). Mutational loss of PTEN induces resistance to NOTCH 1 inhibition in T-cell leukemia. Nature Medicine,13,1203-1210.
Pinnix, C.C., Lee, J.T., Liu, Z.J., McDaid, R., Balint, K., Beverly, L.J., et al. (2009). Active Notch1 confers a transformed phenotype to primary human melanocytes. Cancer Research,69, 5312-5320.
Pillai, R.S., Bhattacharyya, S.N., Filipowicz, W. (2007). Repression of protein synthesis y miRNAs:how many mechanisms? Trends in Cell Biology,17,118-126.
Poirault-Chassac, S., Six, E., Catelain, C., Lavergne,M., Villeval, J.L., Vainchenker, W., et al. (2010). Notch/Delta4 signaling inhibits human megakaryocytic terminal differentiation. Blood, 116,5670-5678.
Rangarajan, A., Talora, C., Okuyama, R., Nicolas, M., Mammucari, C., Oh, H., et al. (2001). Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. The EMBO Journal,20,3427-3436.
Rasul, S., Balasubramanian, R., Filipovic, A., Slade, M.J., Yague, E., Coombes, R.C. (2009). Inhibition of gamma-secretase induces G2/M arrest and triggers apoptosis in breast cancer cells. British Journal of Cancer,100,1879-1888.
Real, P.J., Tosello, V., Palomero, T., Castillo, M., Hernando, E., de Stanchina, E., et al. (2009). Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nature Medicine,15,50-58.
Reizis, B., Leder, P. (2002). Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway. Genes & Development,16,295-300.
Ridgway, J., Zhang, G., Wu, Y., Stawicki, S., Liang, W.C., Chanthery, Y., et al. (2006). Inhibition of DI14 signalling inhibits tumour growth by deregulating angiogenesis. Nature,444, 1083-1087.
Ronchini, C., Capobianco, A.J. (2001). Induction of cyclin D1 transcription and CDK2 activity by Notch(ic):implication for cell cycle disruption in transformation by Notch(ic). Molecular and Cellular Biology,21,5925-5934.
Saito, Y., Murata-Kamiya, N., Hirayama, T., Ohba, Y., Hatakeyama, M. (2010). Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21. Journal of Experimental Medicine,207,2157-74.
Samon, J.B., Castillo-Martin, M., Hadler, M., Ambesi-Impiobato, A., Paietta, E., Racevskis, J., et al. (2012). Preclinical analysis of the y-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Molecular Cancer Therapeutics,11, 1565-1575.
Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B., Cavalli, G. (2007). Genome regulation by polycomb and trithorax proteins. Cell,128,735-745.
Selleck. Ro4929097. http://www.selleckchem.com/products/RO4929097. html (29 April 2013, date last accessed).
Shao, H., Huang, Q., Liu, Z.J. (2012). Targeting Notch signaling for cancer therapeutic intervention. Advances in Pharmacology,65,191-234.
Shelton, C.C., Zhu, L., Chau, D., Yang, L., Wang, R., Djaballah, H., et al. (2009). Modulation of gamma-secretase specificity using small molecule allosteric inhibitors. Proceedings of the National Academy of Sciences of the United States of America,106,20228-20233.
Smith, S.M., Moran, A.P., Duggan, S.P., Ahmed, S.E., Mohamed, A.S., Windle, H.J., et al. (2011). Tribbles 3:a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide. Journal of Immunology,186,2462-71.
Stahl, M., Uemura, K., Ge, C., Shi, S., Tashima, Y., Stanley, P. (2008). Roles of Pofutl and O-fucose in mammalian Notch signaling. Journal of Biological Chemistry,283,13638-13651.
Stead, C.M., Zhao, J., Raetz, C.R., Trent, M.S. (2010). Removal of the outer Kdo from Helicobacter pylori lipopolysaccharide and its impact on the bacterial surface. Molecular Microbiology,78,837-52.
Sycuro, L.K., Pincus, Z., Gutierrez, K.D., Biboy, J., Stern, C.A., Vollmer, W., et al. (2010). Peptidoglycan crosslinking relaxation promotes Helicobacter pylori's helical shape and stomach colonization. Cell,141,822-33.
Tanaka, H., Yoshida, M., Nishiumi, S., Ohnishi, N., Kobayashi, K., Yamamoto, K., et al. (2010). The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice. Archives of Biochemistry and Biophysics,498,35-42.
Tegtmeyer, N., Hartig, R., Delahay, R.M., Rohde, M., Brandt, S., Conradi, J., et al. (2010). A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation. Journal of Biological Chemistry,285,23515-23526.
Tegtmeyer, N., Wessler, S., Backert, S. (2011a). Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. The Federation of European Biochemical Societies Journal,278,1190-1202.
Tegtmeyer, N., Wittelsberger, R., Hartig, R., Wessler, S., Martinez-Quiles, N., Backert, S. (2011b). Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori. Cell Host Microbe,9,520-31.
Thurston, G., Noguera-Troise, I., Yancopoulos, G. D. (2007). The Delta paradox:DLL4 blockade leads to more tumour vessels but less tumour growth. Nature Reviews Cancer,7, 327-331.
van Es, J.H., van Gijn, M.E., Riccio, O., van den Born, M., Vooijs, M., Begthel, H., et al. (2005). Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature,435,959-963.
van Tetering, G., van Diest, P., Verlaan, I., van der Wall, E., Kopan, R., Vooijs, M. (2009). Metal loprotease ADAM10 is required for Notchl site 2 cleavage. Journal of Biological Chemistry 284,31018-31027.
Wallberg, A. E., Pedersen, K., Lendahl, U.,& Roeder, R. G. (2002). p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Molecular and Cellular Biology,22,7812-7819.
Wang, Z., Banerjee, S., Li, Y., Rahman, K. M., Zhang, Y., Sarkar, F. H. (2006a). Downregulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Research,66,2778-2784.
Wang, Z., Zhang, Y., Banerjee, S., Li, Y., Sarkar, F. H. (2006b). Inhibition of nuclear factor kappab activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells. International Journal of Cancer,118,1930-1936.
Wang, Z., Zhang, Y., Banerjee, S., Li, Y., Sarkar, F. H. (2006c). Notch-1 downregulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer,106,2503-2513.
Wang, Z., Li, Y., Banerjee, S., Sarkar, F. H. (2009). Emerging role of Notch in stem cells and cancer. Cancer Letters,279,8-12.
Watanabe, T., Asano, N., Fichtner-Feigl, S., Gorelick, P.L., Tsuji, Y., Matsumoto, Y., et al. (2010). NODI contributes to mouse host defense against Helicobacter pylori via induction of type Ⅰ IFN and activation of the ISGF3 signaling pathway. Journal of Clinical Investigation,120, 1645-1662.
Weng, A.P., Ferrando, A.A., Lee, W., Morris, J.P., Silverman, L.B., Sanchez-Irizarry, C., et al (2004). Activating mutations of NOTCH 1 in human T cell acute lymphoblastic leukemia. Science, 306,269-271.
Weng, A.P., Millholland, J.M., Yashiro-Ohtani, Y., Arcangeli, M.L., Lau, A., Wai, C., et al. (2006). c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes & Development,20,2096-2109.
Weng, A.P., Nam, Y., Wolfe, M.S., Pear, W.S., Griffin, J.D., Blacklow, S.C., et al. (2003). Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Molecular and Cellular Biology,23,655-664.
Wilkin, M.B., Carbery, A.M., Fostier, M., Aslam, H., Mazaleyrat, S.L., Higgs, J., et al. (2004). Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Current Biology,14,2237-2244.
Wilson, J.J.& Kovall, R.A. (2006). Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA. Cell,124,985-996.
Wong, G.T., Manfra, D., Poulet, F.M., Zhang, Q., Josien, H., Bara, T., et al. (2004). Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits betaamyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. Journal of Biological Chemistry,279, 12876-12882.
Wu, L.& Griffin, J.D. (2004). Modulation of Notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis. Seminars in Cancer Biology, 14,348-356.
Wu, Y., Cain-Hom, C., Choy, L., Hagenbeek, T. J., de Leon, G.P., Chen, Y., et al. (2010). Therapeutic antibody targeting of individual Notch receptors. Nature,464,1052-1057.
Yan, M., Callahan, C.A., Beyer, J.C., Allamneni, K.P., Zhang, G., Ridgway, J.B., et al. (2010). Chronic DLL4 blockade induces vascular neoplasms. Nature,463, E6-E7.
Yan, M.& Plowman, G.D. (2007). Delta-like 4/Notch signaling and its therapeutic implications. Clinical Cancer Research,13,7243-7246.
Yao, J.& Qian, C. (2009). Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway. Medical Oncology, 27,1017-1022.
Yeh, Y.C., Chang, W.L., Yang, H.B., Cheng, H.C., Wu, J.J., Sheu, B.S. (2011). Helicobacter pylori CagL amino acid sequence polymorphism Y58E59 induces a corpus shift of gastric integrin a5bl related with gastric carcinogenesis. Molecular Carcinogenesis,50,751-759.
Amsen, D., Blander, J.M., Lee, G.R., Tanigaki, K., Honjo, T., Flavell, R.A. (2004). Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell,117,515-526.
Barten, D. M., Meredith, J. E., Jr., Zaczek, R., Houston, J. G.,& Albright, C. F. (2006). Gamma-secretase inhibitors for Alzheimer's disease:balancing efficacy and toxicity. Drugs in Rerearch and Development,7,87-97.
Beel, A.J., Sanders, C.R. (2008). Substrate specificity of gamma-secretase and other intramembrane proteases. Cellular and Molecular Life Science,65,1311-1334.
Beverly, L.J., Felsher, D.W., Capobianco, A.J. (2005). Suppression of p53 by Notch in lymphomagenesis:implications for initiation and regression. Cancer Resesrch,65,7159-7168.
Borghese, L., Dolezalova, D., Opitz, T., Haupt, S., Leinhaas, A., Steinfarz, B., et al. (2010). Inhibition of Notch Signaling in Human Embryonic Stem Cell-Derived Neural Stem Cells Delays Gl/S Phase Transition and Accelerates Neuronal Differentiation In Vitro and In Vivo. Stem Cells,28,955-964.
Borriello, A., Pietra, V.D., Criscuolo, M., Oliva, A., Tonini, G.P., Iolascon, A., et al. (2000). p27(Kipl) accumulation is associated with retinoic-induced neuroblastoma differentiation: evidence of a decreased proteasome-dependent degradation. Oncogene,19,51-60.
Caruso, R., Fina, D., Peluso, I., Fantini, M.C., Tosti, C., Del Vecchio, B.G., et al. (2007). IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. Journal of Immunology,178,5957-5965.
Chen, X., Zhang, T., Shi, J., Xu, P., Gu, Z., Sandham, A. et al. (2013) Notch1 Signaling Regulates the Proliferation and Self-Renewal of Human Dental Follicle Cells by Modulating the G1/S Phase Transition and Telomerase Activity. PLoS ONE 8(7):e69967. doi:10.1371/journal.pone.0069967
Cho, O.H., Shin, H.M., Miele, L., Golde, T.E., Fauq, A., Minter, L.M., et al. (2009). Notch regulates cytolytic effector function in CD8+ T cells. Journal of Immunology,182,3380-3389.
de Martel, C., Ferlay, J., Franceschi, S., Vignat, J., Bray, F., Forman, D., et al. (2012). Global burden of cancers attributable to infections in 2008:a review and synthetic analysis. Lancet Oncology,13,607-615.
Dirlam, A., Spike, B.T., MacLeod, K.F. (2007). Deregulated E2f-2 underlies cell cycle and maturation defects in retino-blastoma null erythroblasts. Molecular and Cellular Biology,27, 8713-8728.
Ferrand, J., Lehours, P., Schmid-Alliana, A., Megraud, F., Varon, C. (2011). Helicobacter pylori infection of gastrointestinal epithelial cells in vitro induces mesenchymal stem cell migration through an NF-kappaB-dependent pathway. PLoS ONE,6, e29007.
Foo, J.H., Culvenor, J.G., Ferrero, R.L., Kwok, T., Lithgow, T., Gabriel, K. (2010). Both the p33 and p55 subunits of the Helicobacter pylori VacA toxin are targeted to mammalian mitochondria. Journal of Molecular Biology,401,792-798.
Fre, S., Pallavi, S. K., Huyghe, M., Lae, M., Janssen, K.P., Robine, S. et al. (2009). Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proceedings of the National Academy of Sciences of the United States of America,106,6309-6314.
Galmiche, A., Rassow, J. (2010). Targeting of Helicobacter pylori VacA to mitochondria. Gut Microbes,1,392-395.
Gujuluva, C.N., Baek, J.H., Shin, K.H., Cherrick, H.M., Park, N.H. (1994). Effect of UV-irradiation on cell cycle, viability and the expression of p53, gaddl53 and gadd45 genes in normal and HPV-immortalized human oral keratinocytes. Oncogene,9,1819-1827.
Guo, W., Lasky, J.L., Chang, C.J., Mosessian, S., Lewis, X., Xiao, Y., et al. (2008). Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation. Nature 453,529-533.
Hemming, M.L, Elias, J.E., Gygi, S.P., Selkoe, D.J. (2008). Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biology,6, e257.
Herrera, V., Parsonnet, J. (2009). Helicobacter pylori and gastric adenocarcinoma. Clinical Microbiology and Infection,15,971-976.
Hiyama, A., Skubutyte, R., Markova, D., Anderson, D.G., Yadla, S., Sakai, D., et al. (2011). Hypoxia activates the notch signaling pathway in cells of the intervertebral disc:implications in degenerative disc disease. Arthritis & Rheumatology,63,1355-1364.
Ito, T., Schaller, M., Hogaboam, C.M., Standiford, T.J., Sandor, M., Lukacs, N.W., et al. (2009). TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4. Journal of Clinical Investigation,119, 33-46.
Jin, S., Tong, T., Fan, W., Fan, F., Antinore, M.J., Zhu, X., et al. (2002). GADD45-induced cell cycle G2-M arrest associates with altered subcellular distribution of cyclin B1 and is independent of p38 kinase activity. Oncogene,21,8696-8704.
Joshi, I., Minter, L.M., Telfer, J., Demarest, R.M., Capobianco, A.J., Aster, J.C., et al. (2009). Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood,113,1689-1698.
Kastan, M.B., Zhan, Q., el-Deiry, W.S., Carrier, F., Jacks, T., Walsh, W.V., et al. (1992). A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell,71,587-597.
Kim, T.H., Shivdasani, R.A. (2011). Notch signaling in stomach epithelial stem cell homeostasis. Journal of Experimental Medicine,208,677-688.
Kimura, K., Satoh, K., Kanno, A., Hamada, S., Hirota, M., Endoh, M., et al. (2007). Activation of Notch signaling in tumorigenesis of experimental pancreatic cancer induced by dimethylbenzanthracene in mice. Cancer Science,98,155-162.
LaVoie, M. J., Selkoe, D. J. The Notch ligands, Jagged and Delta, are sequentially processed by a-secretase and presenilin/y-secretase and release signaling fragments. Journal of Biological Chemistry,278,34427-34437 (2003).
Lee, I.O., Kim, J.H., Choi, Y.J., Pillinger, M.H., Kim, S.Y., Blaser, M.J., et al. (2010). Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. Journal of Biological Chemistry,285,16042-16050.
Lleo, A. (2008). Activity of gamma-secretase on substrates other than APP. Current Topics in Medicinal Chemistry,8,9-16.
Maekawa, Y., Minato, Y., Ishifune, C., Kurihara, T., Kitamura, A., Kojima, H., et al. (2008). Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nature Immunology,9,1140-1147.
Mukherjee, S., Schaller, M.A., Neupane, R., Kunkel, S.L., Lukacs, N.W. (2009). Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. Journal of Immunology,182,7381-7388.
Mungamuri, S.K., Yang, X., Thor, A.D., Somasundaram, K. (2006). Survival signaling by Notch 1:mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Resesrch, 66,4715-4724.
Nagy, T.A., Frey, M.R., Yan, F., Israel, D.A., Polk, D.B., Peek, Jr R.M. (2009). Helicobacter pylori Regulates Cellular Migration and Apoptosis by Activation of Phosphatidylinositol 3-Kinase Signaling. Journal Of Infectious Diseases,199,641-651.
Nair, P., Somasundaram, K., Krishna, S. (2003). Activated Notch1 inhibits p53-induced apoptosis and sustains transformation by human papillomavirus type 16 E6 and E7 oncogenes through a PI3K-PKB/Aktdependent pathway. Journal of Virology,77,7106-7112.
Noseda, M., Chang, L., McLean, G., Grim, J.E., Clurman, B.E., Smith, L.L., et al. (2004). Notch Activation Induces Endothelial Cell Cycle Arrest and Participates in Contact Inhibition: Role of p21Cip1 Repression. Molecular and Cellular Biology,24,8813-8822.
O'Neil, J., Grim, J., Strack, P., Rao, S., Tibbitts, D., Winter, C., et al. (2007). FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. Journal of Experimental Medicine,204,1813-1824.
Palaga, T., Miele, L., Golde, T.E., Osborne, B.A. (2003). TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells. Journal of Immunology, 171,3019-3024.
Palomero, T., Sulis, M. L., Cortina, M., Real, P. J., Barnes, K., Ciofani, M., et al. (2007). Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nature Medicine,13,1203-1210.
Palomero, T., Dominguez, M., Ferrando, A.A. (2008). The role of the PTEN/AKT pathway in NOTCH1-induced leukemia. Cell Cycle,7,965-970
Polk, D.B.,& Peek, R.M. Jr. (2010). Helicobacter pylori:gastric cancer and beyond. Nature Reviews Cancer,10,403-414.
Radtke, F., Fasnacht, N., MacDonald H. R. (2010). Notch Signaling in the Immune System. Immunity,32,14-27.
Rao, S.S., O'Neil, J., Liberator, C.D., Hardwick, J.S., Dai, X., Zhang, T., et al. (2009). Inhibition of NOTCH Signaling by Gamma Secretase Inhibitor Engages the RB Pathway and Elicits Cell Cycle Exit in T-Cell Acute Lymphoblastic Leukemia Cells. Cancer Resesrch,69, 3060-3068.
Ricci, V., Romano, M., Boquet, P., (2011). Molecular cross-talk between Helicobacter pylori and human gastric mucosa. World Journal of Gastroenterology,17,1383-1399.
Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature, 447,330-333.
Sahlgren, C., Gustafsson, M.V., Jin, S., Poellinger, L., Lendahl U. (2008). Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proceedings of the National Academy of Sciences of the United States of America,105,6392-6397.
Six, E., Ndiaye, D., Laabi, Y., et al. The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and y-secretase. Proceedings of the National Academy of Sciences of the United States of America,100,7638-7643 (2003).
Shi, Y., Liu, X.F., Zhuang, Y., Zhang, J,Y, Liu, T., Yin, Z.N., et al. (2010). Helicobacter pylori-Induced Th17 Responses Modulate Thl Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice. Journal of Immunology,184,5121-5129.
Smith, S.M., Moran, A.P., Duggan, S.P., Ahmed, S.E., Mohamed, A.S., Windle, H.J., et al. (2011). Tribbles 3:a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide. Journal of Immunology,186,2462-2471.
Skokos, D.,& Nussenzweig, M.C. (2007). CD8-DCs induce IL-12-independent Thl differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. Journal of Experimental Medicine,204,1525-1531.
Sun, J., Krawczyk, C.J., Pearce, E.J. (2008). Suppression of Th2 cell development by Notch ligands Deltal and Delta4. Journal of Immunology,180,1655-1661.
Sun, H.W., Wu, C.,,Tan H.Y., Wang,Q.S. (2012). Combination DLL4 with Jagged 1-siRNA can Enhance Inhibition of the Proliferation and Invasiveness Activity of Human Gastric Carcinoma by Notchl/VEGF Pathway. Hepato-Gastroenterology,59,924-929.
Tegtmeyer, N., Hartig, R., Delahay, R.M., Rohde, M., Brandt, S., Conradi, J., et al. (2010). A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation. Journal of Biological Inorganic Chemistry,285,23515-23526.
Tegtmeyer, N., Wessler, S., Backert, S. (2011a). Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. The Federation of European Biochemical Societies Journal,278,1190-1202.
Tegtmeyer, N., Wittelsberger, R., Hartig, R., Wessler, S., Martinez-Quiles, N., Backert, S. (2011b). Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori. Cell Host Microbe,9,520-531.
Tsang, Y.H., Lamb, A., Romero-Gallo, J., Huang, B., Ito, K., Peek, Jr R.M., et al. (2010). Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene,29,5643-5650.
Uren, A.G., Kool, J., Matentzoglu, K., de Ridder, J., Mattison, J., van Uitert, M., et al. (2008). Large-scale mutagenesis in p19(ARF)-and p53-deficient mice identifies cancer genes and their collaborative networks. Cell,133,727-741.
Wang, H., Sun,Y., Liu, S., Yu, H., Li, W., Zeng, J., et al. (2011). Upregulation of progranulin by Helicobacter pylori in humangastric epithelial cellsvia p38MAPK and MEK1/2 signaling pathway:role in epithelial cell proliferationand migration. FEMS Immunology and Medical Microbiology,63,82-92.
Wang, Z., Li, Y., Ahmad, A., Banerjee, S., Azmi, A.S., Kong, D., et al. (2011). Down-regulation of Notch-1 is associated with Akt and FoxMl in inducing cell growth inhibition and apoptosis in prostate cancer cells. Journal of Cellular Biochemistry,112,78-88.
Wang, Z., Parikh, H., Jia, J., Myers, T., Yeager, M., Jacobs, K.B.,et al. (2012). Helicobacter pylori CagA inhibits the expression of Runx3 via Src/MEK/ERK and p38 MAPK pathways in gastric epithelial cell. Journal of Cellular Biochemistry,113,1080-1086.
Watanabe, T., Asano, N., Fichtner-Feigl, S., Gorelick, P.L., Tsuji, Y., Matsumoto, Y., et al. (2010). NODI contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the 1SGF3 signaling pathway. Journal of Clinical Investigation,120, 1645-1662.
Wong, G.T., Manfra, D., Poulet, F.M., Zhang, Q., Josien, H., Bara, T., et al. (2004). Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits betaamyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. Journal of Biological Chemistry,279, 12876-12882.
Yao, J., Qian, C., Shu, T., Zhang, X., Zhao, Z., Liang, Y. (2013). Combination treatment of PD98059 and DAPT in gastric cancer through induction of apoptosis and downregulation of WNT/β-catenin. Cancer Biology & Therapy,14,833-839.
Abcam. DAPT. http://www.abcam.com/DAPT-ab120633.html (29 April 2013, date last accessed).
Amsen, D., Antov, A., Jankovic, D., Sher, A., Radtke, F., Souabni, A., et al. (2007). Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity,27,89-99.
Arora, P. S.& Ansari, A. Z. (2009). Chemical biology:a Notch above other inhibitors. Nature, 462,171-173.
Backert, S.& Naumann, M. (2010). What a disorder:proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiology,18,479-486.
Backert, S., Tegtmeyer, N., Selbach, M. (2010). The versatility of Helicobacter pylori CagA effector protein functions:the master key hypothesis. Helicobacter,15,163-176.
Barry, D.P., Asim, M., Leiman, D.A., de Sablet, T., Singh, K., Casero, R.A., et al. (2011). Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction. PLoS ONE,28, e17510.
Barten, D. M., Meredith, J. E., Jr., Zaczek, R., Houston, J. G., Albright, C. F. (2006). Gamma-secretase inhibitors for Alzheimer's disease:balancing efficacy and toxicity. Drugs in Rerearch and Development,7,87-97.
Bedogni, B., Warneke, J. A., Nickoloff, B. J., Giaccia, A. J., Powell, M. B. (2008). Notchl is an effector of Akt and hypoxia in melanoma development. Journal of Clinical Investigation,118, 3660-3670.
Beel, A.J.& Sanders, C.R. (2008). Substrate specificity of gamma-secretase and other intramembrane proteases. Cellular and Molecular Life Science,65,1311-1334.
Bozkulak, E. C.& Weinmaster, G. (2009). Selective use of ADAM10 and ADAM17 in activation of Notchl signaling. Molecular and Cellular Biology,29,5679-5695.
Brou, C., Logeat, F., Gupta, N., Bessia, C., LeBail, O., Doedens, J. R., et al. (2000). A novel proteolytic cleavage involved in Notch signaling:the role of the disintegrin-metalloprotease TACE. Molecular Cell,5,207-216.
Cavallo, P., Cianciulli, A., Mitolo, V., Panaro, M.A. (2010). Lipopolysaccharide (LPS) of Helicobacter modulates cellular DNA repair systems in intestinal cells. Clinical and Experimental Medicine,11(3),171-179.
Chang, P.C., Wang, C.J., You, C.K., Kao, M.C. (2011). Effects of a HP0859 (rfaD) knockout mutation on lipopolysaccharide structure of Helicobacter pylori 26695 and the bacterial adhesion on AGS cells. Biochemical and Biophysical Research Communications,405,497-502.
Cheng, P., Zlobin, A., Volgina, V., Gottipati, S., Osborne, B., Simel, E. J., et al. (2001). Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. Journal of Immunology, 167,4458-4467.
Children's Oncology Group. (2012) Gamma-secretase inhibitor RO4929097 in treating young patients with relapsed or refractory solid tumors, CNS tumors, lymphoma, or T-cell leukemia (NCT01088763).
Cohen, B., Shimizu, M., Izrailit, J., Ng, N. F., Buchman, Y., Pan, J. G., et al. (2009). Cyclin D1 is a direct target of JAG 1-mediated Notch signaling in breast cancer. Breast Cancer Research and Treatment,123,113-124.
De Koning, L., Corpet, A., Haber, J. E., Almouzni, G. (2007). Histone chaperones:an escort network regulating histone traffic. Nature Structural & Molecular Biology,14,997-1007.
De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., et al. (1999). A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature,398,518-522.
Delwig, A.& Rand, M. D. (2008). Kuz and TACE can activate Notch independent of ligand. Cellular and Molecular Life Science,65,2232-2243.
Ding, S.Z., Fischer, W., Kaparakis-Liaskos, M., Liechti, G., Merrell, D.S., Grant, P.A., et al. (2010).Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS ONE,5, e9875.
Espinosa, L., Ingles-Esteve, J., Aguilera, C., Bigas, A. (2003). Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. Journal of Biological Chemistry,278,32227-32235.
Eitoku, M., Sato, L., Senda, T., Horikoshi, M. (2008). Histone chaperones:30 years from isolation to elucidation of the mechanisms of nucleosome assembly and disassembly. Cellular and Molecular Life Science,65,414-444.
Falk, R., Falk, A., Dyson, M.R., Melidoni, A.N., Parthiban, K., Young, J.L. et al. (2012) Generation of anti-Notch antibodies and their application in blocking Notch signalling in neural stem cells. Methods,58,69-78.
Fontana, J. R.& Posakony, J. W. (2009). Both inhibition and activation of Notch signaling rely on a conserved neuralized-binding motif in bearded proteins and the Notch ligand Delta. Developmental Biology,333,373-385.
Foo, J.H., Culvenor, J.G., Ferrero, R.L., Kwok, T., Lithgow, T., Gabriel, K. (2010). Both the p33 and p55 subunits of the Helicobacter pylori VacA toxin are targeted to mammalian mitochondria. Journal of Molecular Biology,401,792-798.
Galmiche, A.& Rassow, J. (2010).Targeting of Helicobacter pylori Vac A to mitochondria. Gut Microbes,1,392-395.
Garzia, L., Andolfo, I., Cusanelli, E., Marino, N., Petrosino, G., De Martino, D., et al. (2009). MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PLoS One,4, e4998.
Ge, R., Sun, X., Xiao, C., Yin, X., Shan, W., Chen, Z., et al. (2011). Phosphoproteome analysis of the pathogenic bacterium Helicobacter pylori reveals over-representation of tyrosine phosphorylation and multiply phosphorylated proteins. Proteomics,11,1449-1461.
Goodfellow, H., Krejci, A., Moshkin, Y., Verrijzer, C. P., Karch, F., Bray, S. J. (2007). Gene-specific targeting of the histone chaperone asfl to mediate silencing. Developmental Cell, 13,593-600.
Grubman, A., Kaparakis, M., Viala, J., Allison, C., Badea, L., Karrar, A., et al. (2010). The innate immune molecule, NOD1, regulates direct killing of Helicobacter pylori by antimicrobial peptides. Cell Microbiology,12,626-639.
Hallahan, A. R., Pritchard, J. I., Hansen, S., Benson, M., Stoeck, J., Hatton, B. A., et al. (2004). The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Research,64,7794-7800.
He, F., Saito, K., Kobayashi, N., Harada, T., Watanabe, S., Kigawa, T., et al. (2009). Structural and functional characterization of the NHR1 domain of the Drosophila neuralized E3 ligase in the notch signaling pathway. Journal of Molecular Biology,393,478-495.
Hemming, M.L, Elias, J.E., Gygi, S.P., Selkoe, D.J. (2008). Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biology,6, e257.
H. Lee Moffitt Cancer Center and Research Institute. (2012) An open-label study of RO4929097 in metastatic colorectal cancer (NCT01116687).
Hoey, T., Yen, W. C., Axelrod, F., Basi, J., Donigian, L., Dylla, S., et al. (2009). DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell,5, 168-177.
Howells,L.M., Sale, S., Sriramareddy, S.N., Irving, G.R., Jones, D.J., Ottley, C.J.,et al. (2011). Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. International Journal of Cancer,129,476-486.
http://clinicaltrials.gov/ct2/show/NCT00106145
http://clinicaltrials.gov/ct2/show/NCT00878189
Hug, I., Couturier, M.R., Rooker, M.M., Taylor, D.E., Stein, M., Feldman, M.F. (2010). Helicobacter pylori lipopolysaccharide is synthesized via a novel pathway with an evolutionary connection to protein N-glycosylation. Plos Pathogens,6, e1000819.
Hutton, M.L., Kaparakis-Liaskos, M., Turner, L., Cardona, A., Kwok, T., Ferrero, R.L. (2010). Helicobacter pylori exploits cholesterol-rich microdomains for induction of NF-kappaB-dependent responses and peptidoglycan delivery in epithelial cells. Infection and Immunity,78,4523-4531.
Izon, D. J., Aster, J. C., He, Y., Weng, A., Karnell, F. G., Patriub, V., et al. (2002). Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch 1. Immunity,16, 231-243.
Jenkins, D.W., Ross, S., Veldman-Jones, M., Foltz, I.N., Clavette, B.C., Manchulenko, K., et al. (2012). MEDI0639:a novel therapeutic antibody targeting D114 modulates endothelial cell function and angiogenesis in vivo. Molecular Cancer Therapeutics,11,1650-1660.
Ji, Q., Hao, X., Zhang, M., Tang, W., Yang, M., Li, L., et al. (2009). MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PloS One,4, e6816.
Jin, Y. H., Kim, H., Oh, M., Ki, H., Kim, K. (2009). Regulation of Notch1/NICD and Hesl expressions by GSK-3alpha/beta. Molecules and Cells,27,15-19.
Jurik, A., Hausser, E., Kutter, S., Pattis, I., Prassl, S., Weiss, E., et al. (2010). The coupling protein Cagbeta and its interaction partner CagZ are required for type IV secretion of the Helicobacter pylori CagA protein. Infection and Immunity,78,5244-5251.
Kallifatidis, G., Labsch, S., Rausch, V., Mattern, J., Gladkich, J., Moldenhauer, G., et al. (2011). Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Molecular Therapy,19,188-195.
Kawahara, T., Kawaguchi-Ihara, N., Okuhashi, Y., Itoh, M., Nara, N., Tohda, S. (2009). Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells. Anticancer Research,29,4629-4632.
Kondratyev, M., Kreso, A., Hallett, R.M., Girgis-Gabardo, A., Barcelon, M.E., Ilieva, D., et al. (2012). Gamma-secretase inhibitors target tumorinitiating cells in a mouse model of ERBB2 breast cancer. Oncogene,31,93-103.
Krop,I., Demuth, T., Guthrie, T., Wen, P.Y., Mason, W.P., Chinnaiyan, P., et al. (2012). Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. Journal of Clinical Oncology,30, 2307-2313.
Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C., et al. (2001). Nrarp is a novel intracellular component of the Notch signaling pathway. Genes & Development, 15,1885-1899.
Lee, I.O., Kim, J.H., Choi, Y.J., Pillinger, M.H., Kim, S.Y., Blaser, M.J., et al. (2010). Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. Journal of Biological Chemistry,285,16042-16050.
Lewis, H. D., Leveridge, M., Strack, P. R., Haldon, C. D., O'Neil, J., Kim, H., et al. (2007). Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling. Chemistry & Biology,14,209-219.
Lleo, A. (2008). Activity of gamma-secretase on substrates other than APP. Current Topics in Medicinal Chemistry,8,9-16.
Lichtenthaler, S. F., Ida, N., Multhaup, G., Masters, C. L., Beyreuther, K. (1997). Mutations in the transmembrane domain of APP altering gamma-secretase specificity. Biochemistry,36, 15396-15403.
Li, K., Li, Y., Wu, W., Gordon, W. R., Chang, D. W., Lu, M., et al. (2008). Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3 Journal of Biological Chemistry,283,8046-8054.
Li, Y., Guessous, F., Zhang, Y., Dipierro, C., Kefas, B., Johnson, E., et al. (2009). icroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Research,69, 7569-7576.
Li,Y. et al. (2012) Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch-1 signaling. The Federation of European Biochemical Societies Journal,279,2247-2259.
Lin, W.C., Tsai, H.F., Kuo, S.H., Wu, M.S., Lin, C.W., Hsu, P.I., et al. (2010).Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Research,70,5740-5748.
Liu,S.K., Bham, S.A., Fokas, E., Beech, J., Im, J., Cho, S., et al. (2011) Delta-like ligand 4-notch blockade and tumor radiation response. Journal of the National Cancer Institute,103, 1778-1798.
Liu, Z. J., Shirakawa, T., Li, Y., Soma, A., Oka, M., Dotto, G. P., et al. (2003). Regulation of Notch 1 and D114 by vascular endothelial growth factor in arterial endothelial cells:implications for modulating arteriogenesis and angiogenesis. Molecular and Cellular Biology,23,14-25.
Luistro, L., He, W., Smith, M., Packman, K., Vilenchik, M., Carvajal, D., et al. (2009). Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Research,69,7672-7680.
Maillard, I., Weng, A. P., Carpenter, A. C., Rodriguez, C. G., Sai, H., Xu, L., et al. (2004). Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood,104, 1696-1702.
Maraver,A., Fernandez-Marcos, P.J., Herranz, D., Canamero, M., Munoz-Martin, M., et al. (2012). Therapeutic effect of y-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK. Cancer Cell,22,222-234.
Marshall, B. J.& Warren, J. R. (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet,1(8390):1311-1315.
Martinez, A. M., Schuettengruber, B., Sakr, S., Janic, A., Gonzalez, C., Cavalli, G. (2009). Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling. Nature Genetics,41,1076-1082.
Masuda, S., Kumano, K., Suzuki, T., Tomita, T., Iwatsubo, T., Natsugari, H., et al. (2009). Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model. Cancer Science,100,2444-2450.
Medlmmune (2010). A phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of MEDI0639 in advanced solid tumors (NCT01577745).
Mizuma,M., Rasheed, Z.A., Yabuuchi, S., Omura, N., Campbell, N.R., de Wilde, R.F., et al. (2012). The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models. Molecular Cancer Therapeutics,11,1999-2009.
Moellering, R.E., Cornejo, M., Davis, T.N., Del Bianco, C., Aster, J.C., Blacklow, S.C., et al. (2009). Direct inhibition of the NOTCH transcription factor complex. Nature,462,182-188.
Moshkin, Y.M., Kan, T.W., Goodfellow, H., Bezstarosti, K., Maeda, R.K., Pilyugin, M., et al. (2009). Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Molecular Cell,35,782-793.
Mumm, J.S., Schroeter, E.H., Saxena, M.T., Griesemer, A., Tian, X., Pan, D.J., et al. (2000). A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Molecular Cell,5,197-206.
Murata-Kamiya, N., Kikuchi, K., Hayashi, T., Higashi, H., Hatakeyama, M. (2010). Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell Host Microbe,7,399-411.
Nagaraj, R.& Banerjee, U. (2009). Regulation of Notch and wingless signalling by phyllopod, a transcriptional target of the EGFR pathway. The EMBO Journal,28,337-346.
Nam, Y., Sliz, P., Song, L., Aster, J.C., Blacklow, S.C. (2006). Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell,124, 973-983.
Necchi, V., Sommi, P., Ricci, V., Solcia, E. (2010). In vivo accumulation of Helicobacter pylori products, NODI, ubiquitinated proteins and proteasome in a novel cytoplasmic structure. PLoS ONE,5,e9716.
Nefedova, Y., Sullivan, D.M., Bolick, S.C., Dalton, W.S., Gabrilovich, D.I. (2008). Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood,111,2220-2229.
NIH. (2012) Gamma secretase inhibitor. http://clinicaltrials.gov/ct2/results?term=gamma+secretase+inhibitor& Search=Search.
NIH. (2013) Notch inhibitor cancer. http://www.clinicaltrials.gov/ct2/results?term=notch+inhibitor+cancer& Search=Search.
Noguera-Troise, I., Daly, C., Papadopoulos, N.J., Coetzee, S., Boland, P., Gale, N.W., et al. (2006). Blockade of D114 inhibits tumour growth by promoting non-productive angiogenesis. Nature,444,1032-1037.
Okajima, T.& Irvine, K. D. (2002). Regulation of notch signaling by o-linked fucose. Cell, 111,893-904.
O'Neil, J., Calvo, J., McKenna, K., Krishnamoorthy, V., Aster, J.C., Bassing, C.H., et al. (2006). Activating Notchl mutations in mouse models of T-ALL. Blood,107,781-785.
O'Neil, J., Grim, J., Strack, P., Rao, S., Tibbitts, D., Winter, C., et al. (2007). FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. Journal of Experimental Medicine,204,1813-1824.
Ono, Y., Gnocchi, V.F., Zammit, P.S., Nagatomi, R. (2009). Presenilin-1 acts via Idl to regulate the function of muscle satellite cells in a gamma-secretase-independent manner. Journal of Cell Science,122,4427-4438.
Olbermann, P., Josenhans, C., Moodley, Y., Uhr, M., Stamer, C., Vauterin, M., et al. (2010). A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLOS Genetics,6, e1001069.
Pelz, C., Steininger, S., Weiss, C., Coscia, F., Vogelmann, R. (2011). A novel inhibitory domain of Helicobacter pylori protein CagA reduces CagA effects on host cell biology. Journal of Biological Chemistry,286,8999-9008.
Radin, J.N., Gonza'lez-Rivera, C., Ivie, S.E., McClain, M.S., Cover, T.L. (2011). Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells. Infection and Immunity,79,2535-2543.
Palomero, T., Dominguez, M., Ferrando, A. A. (2008). The role of the PTEN/AKT pathway in NOTCH 1-induced leukemia. Cell Cycle,7,965-970.
Palomero, T., Sulis, M.L., Cortina, M., Real, P.J., Barnes, K., Ciofani, M., et al. (2007). Mutational loss of PTEN induces resistance to NOTCH 1 inhibition in T-cell leukemia. Nature Medicine,13,1203-1210.
Pinnix, C.C., Lee, J.T., Liu, Z.J., McDaid, R., Balint, K., Beverly, L.J., et al. (2009). Active Notch1 confers a transformed phenotype to primary human melanocytes. Cancer Research,69, 5312-5320.
Pillai, R.S., Bhattacharyya, S.N., Filipowicz, W. (2007). Repression of protein synthesis y miRNAs:how many mechanisms? Trends in Cell Biology,17,118-126.
Poirault-Chassac, S., Six, E., Catelain, C., Lavergne,M., Villeval, J.L., Vainchenker, W., et al. (2010). Notch/Delta4 signaling inhibits human megakaryocytic terminal differentiation. Blood, 116,5670-5678.
Rangarajan, A., Talora, C., Okuyama, R., Nicolas, M., Mammucari, C., Oh, H., et al. (2001). Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. The EMBO Journal,20,3427-3436.
Rasul, S., Balasubramanian, R., Filipovic, A., Slade, M.J., Yague, E., Coombes, R.C. (2009). Inhibition of gamma-secretase induces G2/M arrest and triggers apoptosis in breast cancer cells. British Journal of Cancer,100,1879-1888.
Real, P.J., Tosello, V., Palomero, T., Castillo, M., Hernando, E., de Stanchina, E., et al. (2009). Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nature Medicine,15,50-58.
Reizis, B., Leder, P. (2002). Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway. Genes & Development,16,295-300.
Ridgway, J., Zhang, G., Wu, Y., Stawicki, S., Liang, W.C., Chanthery, Y., et al. (2006). Inhibition of DI14 signalling inhibits tumour growth by deregulating angiogenesis. Nature,444, 1083-1087.
Ronchini, C., Capobianco, A.J. (2001). Induction of cyclin D1 transcription and CDK2 activity by Notch(ic):implication for cell cycle disruption in transformation by Notch(ic). Molecular and Cellular Biology,21,5925-5934.
Saito, Y., Murata-Kamiya, N., Hirayama, T., Ohba, Y., Hatakeyama, M. (2010). Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21. Journal of Experimental Medicine,207,2157-74.
Samon, J.B., Castillo-Martin, M., Hadler, M., Ambesi-Impiobato, A., Paietta, E., Racevskis, J., et al. (2012). Preclinical analysis of the y-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Molecular Cancer Therapeutics,11, 1565-1575.
Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B., Cavalli, G. (2007). Genome regulation by polycomb and trithorax proteins. Cell,128,735-745.
Selleck. Ro4929097. http://www.selleckchem.com/products/RO4929097. html (29 April 2013, date last accessed).
Shao, H., Huang, Q., Liu, Z.J. (2012). Targeting Notch signaling for cancer therapeutic intervention. Advances in Pharmacology,65,191-234.
Shelton, C.C., Zhu, L., Chau, D., Yang, L., Wang, R., Djaballah, H., et al. (2009). Modulation of gamma-secretase specificity using small molecule allosteric inhibitors. Proceedings of the National Academy of Sciences of the United States of America,106,20228-20233.
Smith, S.M., Moran, A.P., Duggan, S.P., Ahmed, S.E., Mohamed, A.S., Windle, H.J., et al. (2011). Tribbles 3:a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide. Journal of Immunology,186,2462-71.
Stahl, M., Uemura, K., Ge, C., Shi, S., Tashima, Y., Stanley, P. (2008). Roles of Pofutl and O-fucose in mammalian Notch signaling. Journal of Biological Chemistry,283,13638-13651.
Stead, C.M., Zhao, J., Raetz, C.R., Trent, M.S. (2010). Removal of the outer Kdo from Helicobacter pylori lipopolysaccharide and its impact on the bacterial surface. Molecular Microbiology,78,837-52.
Sycuro, L.K., Pincus, Z., Gutierrez, K.D., Biboy, J., Stern, C.A., Vollmer, W., et al. (2010). Peptidoglycan crosslinking relaxation promotes Helicobacter pylori's helical shape and stomach colonization. Cell,141,822-33.
Tanaka, H., Yoshida, M., Nishiumi, S., Ohnishi, N., Kobayashi, K., Yamamoto, K., et al. (2010). The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice. Archives of Biochemistry and Biophysics,498,35-42.
Tegtmeyer, N., Hartig, R., Delahay, R.M., Rohde, M., Brandt, S., Conradi, J., et al. (2010). A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation. Journal of Biological Chemistry,285,23515-23526.
Tegtmeyer, N., Wessler, S., Backert, S. (2011a). Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. The Federation of European Biochemical Societies Journal,278,1190-1202.
Tegtmeyer, N., Wittelsberger, R., Hartig, R., Wessler, S., Martinez-Quiles, N., Backert, S. (2011b). Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori. Cell Host Microbe,9,520-31.
Thurston, G., Noguera-Troise, I., Yancopoulos, G. D. (2007). The Delta paradox:DLL4 blockade leads to more tumour vessels but less tumour growth. Nature Reviews Cancer,7, 327-331.
van Es, J.H., van Gijn, M.E., Riccio, O., van den Born, M., Vooijs, M., Begthel, H., et al. (2005). Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature,435,959-963.
van Tetering, G., van Diest, P., Verlaan, I., van der Wall, E., Kopan, R., Vooijs, M. (2009). Metal loprotease ADAM10 is required for Notchl site 2 cleavage. Journal of Biological Chemistry 284,31018-31027.
Wallberg, A. E., Pedersen, K., Lendahl, U.,& Roeder, R. G. (2002). p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Molecular and Cellular Biology,22,7812-7819.
Wang, Z., Banerjee, S., Li, Y., Rahman, K. M., Zhang, Y., Sarkar, F. H. (2006a). Downregulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Research,66,2778-2784.
Wang, Z., Zhang, Y., Banerjee, S., Li, Y., Sarkar, F. H. (2006b). Inhibition of nuclear factor kappab activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells. International Journal of Cancer,118,1930-1936.
Wang, Z., Zhang, Y., Banerjee, S., Li, Y., Sarkar, F. H. (2006c). Notch-1 downregulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer,106,2503-2513.
Wang, Z., Li, Y., Banerjee, S., Sarkar, F. H. (2009). Emerging role of Notch in stem cells and cancer. Cancer Letters,279,8-12.
Watanabe, T., Asano, N., Fichtner-Feigl, S., Gorelick, P.L., Tsuji, Y., Matsumoto, Y., et al. (2010). NODI contributes to mouse host defense against Helicobacter pylori via induction of type Ⅰ IFN and activation of the ISGF3 signaling pathway. Journal of Clinical Investigation,120, 1645-1662.
Weng, A.P., Ferrando, A.A., Lee, W., Morris, J.P., Silverman, L.B., Sanchez-Irizarry, C., et al (2004). Activating mutations of NOTCH 1 in human T cell acute lymphoblastic leukemia. Science, 306,269-271.
Weng, A.P., Millholland, J.M., Yashiro-Ohtani, Y., Arcangeli, M.L., Lau, A., Wai, C., et al. (2006). c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes & Development,20,2096-2109.
Weng, A.P., Nam, Y., Wolfe, M.S., Pear, W.S., Griffin, J.D., Blacklow, S.C., et al. (2003). Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Molecular and Cellular Biology,23,655-664.
Wilkin, M.B., Carbery, A.M., Fostier, M., Aslam, H., Mazaleyrat, S.L., Higgs, J., et al. (2004). Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Current Biology,14,2237-2244.
Wilson, J.J.& Kovall, R.A. (2006). Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA. Cell,124,985-996.
Wong, G.T., Manfra, D., Poulet, F.M., Zhang, Q., Josien, H., Bara, T., et al. (2004). Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits betaamyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. Journal of Biological Chemistry,279, 12876-12882.
Wu, L.& Griffin, J.D. (2004). Modulation of Notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis. Seminars in Cancer Biology, 14,348-356.
Wu, Y., Cain-Hom, C., Choy, L., Hagenbeek, T. J., de Leon, G.P., Chen, Y., et al. (2010). Therapeutic antibody targeting of individual Notch receptors. Nature,464,1052-1057.
Yan, M., Callahan, C.A., Beyer, J.C., Allamneni, K.P., Zhang, G., Ridgway, J.B., et al. (2010). Chronic DLL4 blockade induces vascular neoplasms. Nature,463, E6-E7.
Yan, M.& Plowman, G.D. (2007). Delta-like 4/Notch signaling and its therapeutic implications. Clinical Cancer Research,13,7243-7246.
Yao, J.& Qian, C. (2009). Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway. Medical Oncology, 27,1017-1022.
Yeh, Y.C., Chang, W.L., Yang, H.B., Cheng, H.C., Wu, J.J., Sheu, B.S. (2011). Helicobacter pylori CagL amino acid sequence polymorphism Y58E59 induces a corpus shift of gastric integrin a5bl related with gastric carcinogenesis. Molecular Carcinogenesis,50,751-759.
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