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
Authors: Shijuan Mai
Hsiangfu Kung
Xiaoxia Huang
Jiewei Chen
Yanhui Liu
Fangjian Zhou
Yiji Liao
Jiaxing Zhang
Jianye Liu
Muyan Cai
Yonghong Li
Yixin Zeng
Dan Xie
Journal: European Journal of Cancer (2014)
Discipline: CLINICAL MEDICINE
Keywords: Bladder urothelial carcinoma; E-cadherin; Invasion/metastasis; Prognosis; α4.
Affiliations: 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., 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., 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, Guangdong Provincial People's Hospital, Guangdong, Guangzhou 510080, China., Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, Guangzhou 510080, China., 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: ., 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: .

Abstract:  Aim: 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&lt;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&lt;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. 

Retracted: No

PubPeer comments:
 Fig. 3A and Fig. 5D. After flipping, two WB bands appear more similar than expected. ![file] , 
 In addition to the above, would the authors also be so kind to clarify the identical sections in their scratch assay images depicting the effects of different shRNA constructs? ![file] Aided by ImageTwin ,