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Cytotoxic necrotizing factor 1 promotes prostate cancer progression through activating the Cdc42–PAK1 axis
Author(s) -
Guo Yaxiu,
Zhang Zhisong,
Wei Huiting,
Wang Jingyu,
Lv Junqiang,
Zhang Kai,
Keller Evan T,
Yao Zhi,
Wang Quan
Publication year - 2017
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4940
Subject(s) - cdc42 , pak1 , carcinogenesis , prostate cancer , cancer research , metastasis , tumor progression , cancer , biology , cytotoxic t cell , rac1 , phosphorylation , immunology , signal transduction , in vitro , microbiology and biotechnology , genetics
Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections and plays a role in prostatic carcinogenesis and prostate cancer (PCa) progression. However, the mechanisms through which UPEC promotes PCa development and progression are unclear. Cytotoxic necrotizing factor 1 (CNF1) is one of the most important UPEC toxins and its role in PCa progression has never been studied. We found that UPEC‐secreted CNF1 promoted the migration and invasion of PCa cells and PCa metastasis. In vitro studies showed that CNF1 promotes pro‐migratory and pro‐invasive activity through entering PCa cells and activating Cdc42, which subsequently induced PAK1 phosphorylation and up‐regulation of MMP‐9 expression. CNF1 also promoted pulmonary metastasis in a xenograft mouse model through these mechanisms. PAK1 phosphorylation correlated with advanced grades of PCa in human clinical PCa tissues. These results suggest that CNF1 derived from UPEC plays an important role in PCa progression through activating a Cdc42–PAK1 signal axis and up‐regulating the expression of MMP‐9. Therefore, surveillance for and treatment of cnf1 ‐carrying UPEC strains may diminish PCa progression and thus have an important clinical therapeutic impact. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.