title: α4 contributes to bladder urothelial carcinoma cell invasion and/or metastasis via regulation of E-cadherin and is a predictor of outcome in bladder urothelial carcinoma patients.
abstract: OBJECTIVE
  α4 is upregulated in several types of human cancer and possesses an oncogenic role. However, the abnormalities of α4 and its underlying mechanisms in the pathogenesis of bladder urothelial carcinoma (BUC) remain unknown.
  
  
  METHODS
  α4 expression profile was examined by reverse transcription polymerase chain reaction, western blotting and immunohistochemistry (IHC) in BUC tissues and normal urothelial bladder epithelial tissues. Short hairpin RNA (ShRNA) interfering approach was employed to suppress endogenous α4 expression in BUC cells to determine its role in tumourigenesis, invasion/metastasis and the potential mechanism.
  
  
  RESULTS
  α4 expression in BUC was significantly up-regulated at both mRNA and protein levels compared with that in normal urothelial bladder epithelial tissues. High expression of α4 was inversely correlated with poor survival of the BUC patients (P<0.05). Down-regulation of α4 in BUC EJ and T24 cells led to a G1 phase cell cycle arrest, suppressed cell growth, markedly inhibited invasive motility in vitro and metastatic potential in vivo. Moreover, down-regulation of α4 was found to increase E-cadherin expression and reduce metastasis-associated protein 1 (MTA1) expression either in transcript or protein levels. Importantly, a significant correlation between high expression of α4 and negative expression of E-cadherin in BUC cohorts was observed (P<0.001).
  
  
  CONCLUSIONS
  These findings suggest a potential important role of α4 in control of cell migration and/or invasion via the regulation of E-cadherin expression, and the high α4 expression, as examined by IHC, is an independent molecular marker for shortened survival time of patients with BUC.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Urology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China.
authors.forename: Muyan
authors.initials: M
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China.
authors.forename: Yiji
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China.
authors.forename: Shijuan
authors.initials: S
authors.lastname: Mai
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Urology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathology, Guangdong Provincial People's Hospital, Guangdong, Guangzhou 510080, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, Guangzhou 510080, China.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China.
authors.forename: Hsiangfu
authors.initials: H
authors.lastname: Kung
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Urology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China. Electronic address: zhoufj@sysucc.org.cn.
authors.forename: Fangjian
authors.initials: F
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China. Electronic address: xied@mail.sysu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008222:Lymphokines; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C490467:IGBP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008222:Lymphokines; D018832:Molecular Chaperones; C013059:immunoglobulin-binding factors
keywords: Bladder urothelial carcinoma; E-cadherin; Invasion/metastasis; Prognosis; α4