Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3β/Snail signaling
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en induisant une transition épithélio-mésenchymateuse et l'activation de la signalisation Akt/GSK-3β/Snail, la petite GTPase Rab25 favorise le processus métastatique d'un cancer de la vessie
Rab25, an epithelial-specific member of the Rab family of small GTPases, 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 polymerase chain reaction, 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 mRNA and protein levels in BCs compared to normal bladder tissues. High Rab25 expression was closely associated with lymph node metastasis and was an independent predictor for poor disease-free survival in BC patients. Down-regulation of Rab25 in bladder cancer cells markedly inhibited invasive motility in vitro and metastatic potential in vivo. In addition, down-regulation of Rab25 in bladder cancer EJ and T24 cells increased the expression levels of epithelial markers (E-cadherin and ά-catenin) and decreased the levels of mechamechy markers (vimentin and fibronectin). Simultaneously, down-regulation of Rab25 in EJ and T24 cells resulted in the inactivation of downstream phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-beta (p-GSK-3β) and snail signalling. This study demonstrates that Rab25 can promote BC metastasis through induction of EMT process and activation of Akt/GSK-β/Snail signaling pathway, Rab25 expression level can predict lymph node metastasis and inferior clinical outcome in BC patients.
http://carcin.oxfordjournals.org/content/early/2013/05/29/carcin.bgt187.abstract