Journal
CARCINOGENESIS
Volume 34, Issue 10, Pages 2401-2408Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgt187
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [30900539, 81172429]
- Fundamental Research Funds for the Central Universities [09ykpy35]
- Science and Information Technology Foundation of Guangzhou [2011J2200065]
Ask authors/readers for more resources
Rab25, an epithelial-specific member of the Rab family of small guanosine triphosphatases, is associated with several human cancers. The goal of this study was to determine its function in bladder cancer (BC). We examined the Rab25 expression pattern in two different cohorts of BC patients treated with radical cystectomy by quantitative PCR, western blotting and immunohistochemical staining. A series of in vitro and in vivo assays were performed to elucidate the function of Rab25 in BC and its underlying mechanisms. Rab25 expression was significantly elevated at both the messenger RNA and protein levels in BCs compared with normal bladder tissues. High Rab25 expression was closely associated with lymph node (LN) metastasis and was an independent predictor for poor disease-free survival in BC patients. Downregulation of Rab25 in BC cells markedly inhibited invasive motility in vitro and metastatic potential in vivo. In addition, downregulation of Rab25 in BC EJ and T24 cells increased the expression levels of epithelial markers (E-cadherin and -catenin) and decreased the levels of mechamechy markers (vimentin and fibronectin). Simultaneously, downregulation of Rab25 in EJ and T24 cells resulted in the inactivation of downstream phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase- (p-GSK-3) and snail signaling. This study demonstrates that Rab25 can promote BC metastasis through induction of epithelialmesenchymal transition process and activation of Akt/GSK-3/Snail signaling pathway; Rab25 expression level can predict LN metastasis and inferior clinical outcome in BC patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available