2. Academic Validation
  3. Cytotoxic necrotizing factor 1 promotes prostate cancer progression through activating the Cdc42-PAK1 axis

Cytotoxic necrotizing factor 1 promotes prostate cancer progression through activating the Cdc42-PAK1 axis

  • J Pathol. 2017 Oct;243(2):208-219. doi: 10.1002/path.4940.
Yaxiu Guo 1,  Zhisong Zhang 2,  Huiting Wei 1,  Jingyu Wang 1,  Junqiang Lv 1,  Kai Zhang 3 4,  Evan T Keller 5,  Zhi Yao 1 3,  Quan Wang 1
Affiliations

Affiliations

  • 1 Department of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, PR China.
  • 2 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, PR China.
  • 3 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Tianjin, PR China.
  • 4 Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, PR China.
  • 5 Department of Urology, University of Michigan, Ann Arbor, Michigan, USA.
PMID: 28707808 DOI: 10.1002/path.4940
Abstract

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.

Keywords

Cdc42; PAK1; cytotoxic necrotizing factor 1; prostate cancer; uropathogenic Escherichia coli.

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