title: Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3β/Snail signaling.
abstract: 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 α-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-β (p-GSK-3β) and snail signaling. This study demonstrates that Rab25 can promote BC metastasis through induction of epithelial-mesenchymal transition process and activation of Akt/GSK-3β/Snail signaling pathway; Rab25 expression level can predict LN metastasis and inferior clinical outcome in BC patients.
authors.affiliation: Department of Urology and.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Zhuting
authors.initials: Z
authors.lastname: Tong
authors.forename: Bing
authors.initials: B
authors.lastname: Liao
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Huang
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Junhang
authors.initials: J
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C509763:Rab25 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D020691:rab GTP-Binding Proteins