The role of DAB2IP in androgen receptor activation during prostate cancer progression

Abstract

Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP−/− mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa.

DOI: 10.1038/onc.2013.143
05010015020132014201520162017
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@article{Wu2014TheRO, title={The role of DAB2IP in androgen receptor activation during prostate cancer progression}, author={Karin C Wu and Jun Liu and S C Tseng and Crystal Gore and Z Ning and Nima Sharifi and Ladan Fazli and M. E. Gleave and Payel Kapur and G Xiao and Xiao Sun and Orhan K. Oz and Wexian Min and George Alexandrakis and C J Yang and C R Hsieh and H Q Wu and Dongmei He and Dong H. Xie and J T Hsieh}, journal={Oncogene}, year={2014}, volume={33}, pages={1954-1963} }