Cytotoxic Necrotizing Factor 1 Promotes the Migration and Invasion of Prostate Cancer Cells Through Activating the Cdc42-PAK1 Axis
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- 英文论文题名：Cytotoxic Necrotizing Factor 1 Promotes the Migration and Invasion of Prostate Cancer Cells Through Activating the Cdc42-PAK1 Axis
- 论文作者：Quan Wang
- 英文论文作者：Quan Wang ; Department of Immunology ; School of Basic Medical Sciences ; Tianjin Medical University
- 年：2016
- 作者机构：Department of Immunology,School of Basic Medical Sciences,Tianjin Medical University;
- 英文论文关键词：Cytotoxic Necrotizing Factor 1 ; Uropathogenic Escherichia coli ; Prostate Cancer ; Cdc42 ; PAK1
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R737.25
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：1381k
- 原文格式：D
- 会议级别：全国
摘要
Objective: Urinary tract infections(UTIs) are one of the commonest bacterial infections in humans, and uropathogenic Escherichia coli(UPEC) is the leading cause of UTIs. UPEC can induce cystitis, pyelonephritis and prostatitis, and has also been reported to play a role in prostatic carcinogenesis and prostate cancer(PCa) progression. The mechanisms through which UPEC promotes PCa development and progression are not clear, and the direct influence of UPEC toxins on PCa has not been previously reported. Cytotoxic necrotizing factor 1(CNF1) is a key UPEC toxin, and influences cytoskeleton dynamics and organization of host epithelial cells by activating Rho GTPases, thus we explored if it hadan effect on PCa progression.Methods: Transwell assays were used to examine the migration and invasion ability of prostate cancer cells promoted by CNF1 in vitro. A xenograft mice model was used to examine the metastasis of prostate cancer cells promoted by CNF1 in vivo. Western blotting and RNAinterference were used to study the signal pathways.Results: UPEC-secreted CNF1 promoted the migration and the invasion of PCa cells in vitro and in vivo. Among the three Rho GTPases activated by CNF1, Cdc42 was identified to be responsible for the pro-migratory and pro-invasive effects of CNF1 on PCa cells. We also found active Cdc42 stimulated PAK1 phosphorylation, and active PAK1 upregulated MMP-9 expression, which are essential for CNF1 driving migration and invasion of PCa cells.Conclusions: UPEC-secreted CNF1 promoted the migration and invasion of PCa cells in vitro and in vivo through activating a Cdc42-PAK1 signal axis and upregulating the secretion of MMP-9. Surveillance for and treatment of cnf1-carrying UPEC strains may diminish PCa progression and thus have an important clinical therapeutic impact.
Objective: Urinary tract infections(UTIs) are one of the commonest bacterial infections in humans, and uropathogenic Escherichia coli(UPEC) is the leading cause of UTIs. UPEC can induce cystitis, pyelonephritis and prostatitis, and has also been reported to play a role in prostatic carcinogenesis and prostate cancer(PCa) progression. The mechanisms through which UPEC promotes PCa development and progression are not clear, and the direct influence of UPEC toxins on PCa has not been previously reported. Cytotoxic necrotizing factor 1(CNF1) is a key UPEC toxin, and influences cytoskeleton dynamics and organization of host epithelial cells by activating Rho GTPases, thus we explored if it hadan effect on PCa progression.Methods: Transwell assays were used to examine the migration and invasion ability of prostate cancer cells promoted by CNF1 in vitro. A xenograft mice model was used to examine the metastasis of prostate cancer cells promoted by CNF1 in vivo. Western blotting and RNAinterference were used to study the signal pathways.Results: UPEC-secreted CNF1 promoted the migration and the invasion of PCa cells in vitro and in vivo. Among the three Rho GTPases activated by CNF1, Cdc42 was identified to be responsible for the pro-migratory and pro-invasive effects of CNF1 on PCa cells. We also found active Cdc42 stimulated PAK1 phosphorylation, and active PAK1 upregulated MMP-9 expression, which are essential for CNF1 driving migration and invasion of PCa cells.Conclusions: UPEC-secreted CNF1 promoted the migration and invasion of PCa cells in vitro and in vivo through activating a Cdc42-PAK1 signal axis and upregulating the secretion of MMP-9. Surveillance for and treatment of cnf1-carrying UPEC strains may diminish PCa progression and thus have an important clinical therapeutic impact.
Objective: Urinary tract infections(UTIs) are one of the commonest bacterial infections in humans, and uropathogenic Escherichia coli(UPEC) is the leading cause of UTIs. UPEC can induce cystitis, pyelonephritis and prostatitis, and has also been reported to play a role in prostatic carcinogenesis and prostate cancer(PCa) progression. The mechanisms through which UPEC promotes PCa development and progression are not clear, and the direct influence of UPEC toxins on PCa has not been previously reported. Cytotoxic necrotizing factor 1(CNF1) is a key UPEC toxin, and influences cytoskeleton dynamics and organization of host epithelial cells by activating Rho GTPases, thus we explored if it hadan effect on PCa progression.Methods: Transwell assays were used to examine the migration and invasion ability of prostate cancer cells promoted by CNF1 in vitro. A xenograft mice model was used to examine the metastasis of prostate cancer cells promoted by CNF1 in vivo. Western blotting and RNAinterference were used to study the signal pathways.Results: UPEC-secreted CNF1 promoted the migration and the invasion of PCa cells in vitro and in vivo. Among the three Rho GTPases activated by CNF1, Cdc42 was identified to be responsible for the pro-migratory and pro-invasive effects of CNF1 on PCa cells. We also found active Cdc42 stimulated PAK1 phosphorylation, and active PAK1 upregulated MMP-9 expression, which are essential for CNF1 driving migration and invasion of PCa cells.Conclusions: UPEC-secreted CNF1 promoted the migration and invasion of PCa cells in vitro and in vivo through activating a Cdc42-PAK1 signal axis and upregulating the secretion of MMP-9. Surveillance for and treatment of cnf1-carrying UPEC strains may diminish PCa progression and thus have an important clinical therapeutic impact.
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