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

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.

• Authors: Yifeng Jing, Di Cui, Wenhuan Guo, Juntao Jiang, Bo Jiang, Youyi Lu, Wei Zhao, Xiaohai Wang, Qi Jiang, Bangmin Han, Shujie Xia
• Journal: Cancer letters (Cancer Lett) Vol. 348 Issue 1-2 Pg. 135-45 (Jun 28 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 24662746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

• 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, metabolism)
• Snail Family Transcription Factors
• Transcription Factors (genetics, metabolism)
• Transfection
• Urinary Bladder Neoplasms (genetics, metabolism, pathology)
• Wnt Signaling Pathway
• beta Catenin (metabolism)