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Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC
- Source :
- The FASEB Journal. 34:7927-7940
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract infections, is associated with prostate and bladder cancers. Cytotoxic necrotizing factor 1 (CNF1) is a key UPEC toxin; however, its role in bladder cancer is unknown. In the present study, we found CNF1 induced bladder cancer cells to secrete vascular endothelial growth factor (VEGF) through activating Ras homolog family member C (RhoC), leading to subsequent angiogenesis in the bladder cancer microenvironment. We then investigated that CNF1-mediated RhoC activation modulated the stabilization of hypoxia-inducible factor 1α (HIF1α) to upregulate the VEGF. We demonstrated in vitro that active RhoC increased heat shock factor 1 (HSF1) phosphorylation, which induced the heat shock protein 90α (HSP90α) expression, leading to stabilization of HIF1α. Active RhoC elevated HSP90α, HIF1α, VEGF expression, and angiogenesis in the human bladder cancer xenografts. In addition, HSP90α, HIF1α, and VEGF expression were also found positively correlated with the human bladder cancer development. These results provide a potential mechanism through which UPEC contributes to bladder cancer progression, and may provide potential therapeutic targets for bladder cancer.
- Subjects :
- 0301 basic medicine
Neutrophils
Angiogenesis
Bacterial Toxins
Urinary Bladder
RhoC
Mice, Nude
urologic and male genital diseases
Biochemistry
Cell Line
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Prostate
Heat shock protein
Tumor Microenvironment
Genetics
Animals
Humans
Medicine
HSF1
Molecular Biology
Escherichia coli Infections
Mice, Inbred BALB C
Bladder cancer
Neovascularization, Pathologic
biology
business.industry
Escherichia coli Proteins
Cancer
medicine.disease
female genital diseases and pregnancy complications
Vascular endothelial growth factor
HEK293 Cells
030104 developmental biology
medicine.anatomical_structure
Urinary Bladder Neoplasms
chemistry
rhoC GTP-Binding Protein
Urinary Tract Infections
Cancer research
biology.protein
business
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....3426c522214be54f0d8eb88e74432808