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

K. Wu, J. Liu, S. F. Tseng, C. Gore, Z. Ning, N. Sharifi, L. Fazli, M. Gleave, P. Kapur, G. Xiao, X. Sun, O. K. Oz, W. Min, G. Alexandrakis, C. R. Yang, C. L. Hsieh, H. C. Wu, D. He, D. Xie, J. T. Hsieh

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33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1954-1963
Number of pages10
JournalOncogene
Volume33
Issue number15
DOIs
Publication statusPublished - Apr 10 2014
Externally publishedYes

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Keywords

  • androgen receptor
  • DAB2IP
  • genomic pathway
  • prostate cancer
  • Src

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Wu, K., Liu, J., Tseng, S. F., Gore, C., Ning, Z., Sharifi, N., Fazli, L., Gleave, M., Kapur, P., Xiao, G., Sun, X., Oz, O. K., Min, W., Alexandrakis, G., Yang, C. R., Hsieh, C. L., Wu, H. C., He, D., Xie, D., & Hsieh, J. T. (2014). The role of DAB2IP in androgen receptor activation during prostate cancer progression. Oncogene, 33(15), 1954-1963. https://doi.org/10.1038/onc.2013.143