Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition

Yifeng Jing; Di Cui; Wenhuan Guo; Juntao Jiang; Bo Jiang; Youyi Lu; Wei Zhao; Xiaohai Wang; Qi Jiang; Bangmin Han; Shujie Xia

doi:10.1016/j.canlet.2014.03.018

Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition

Cancer Lett. 2014 Jun 28;348(1-2):135-45. doi: 10.1016/j.canlet.2014.03.018. Epub 2014 Mar 21.

Authors

Yifeng Jing¹, Di Cui¹, Wenhuan Guo², Juntao Jiang¹, Bo Jiang¹, Youyi Lu¹, Wei Zhao¹, Xiaohai Wang¹, Qi Jiang¹, Bangmin Han³, Shujie Xia⁴

Affiliations

¹ Department of Urology, The Affiliated First People's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Pathology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Urology, The Affiliated First People's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: hanbm@163.com.
⁴ Department of Urology, The Affiliated First People's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: xsjurologist@163.com.

PMID: 24662746
DOI: 10.1016/j.canlet.2014.03.018

Abstract

Androgen receptor (AR) has been indicated to be involved in bladder cancer progression. We showed androgen induced epithelial-mesenchymal transition (EMT) in AR-positive bladder cancer cells and promoted tumor metastasis in xenograft models. We subsequently identified that Slug was the mediator of EMT induced by androgen. Furthermore, upregulation of Slug was due to activation of Wnt/β-catenin signaling in response to androgen. Finally, expression of AR showed strong correlation with loss of E-cadherin, higher expression of Slug and nuclear accumulation of β-catenin in bladder tumor tissues. Taken together, our results suggest AR signaling promotes bladder cancer metastasis through Slug mediated EMT.

Keywords: Androgen receptor; Bladder cancer; Epithelial-mesenchymal transition; Slug.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
Animals
Antigens, CD
Cadherins / metabolism
Cell Line, Tumor
Cell Movement
Epithelial-Mesenchymal Transition*
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
RNA Interference
Receptors, Androgen / genetics
Receptors, Androgen / metabolism*
Snail Family Transcription Factors
Transcription Factors / genetics
Transcription Factors / metabolism*
Transfection
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / pathology
Wnt Signaling Pathway
beta Catenin / metabolism

Substances

AR protein, human
Antigens, CD
CDH1 protein, human
CTNNB1 protein, human
Cadherins
Receptors, Androgen
SNAI1 protein, human
Snai2 protein, mouse
Snail Family Transcription Factors
Transcription Factors
beta Catenin