The role of homeostatic regulation between tumor suppressor DAB2IP and oncogenic Skp2 in prostate cancer growth

Yuh Shyan Tsai, Chen Li Lai, Chih Ho Lai, Kai Hsiung Chang, Kaijie Wu, Shu Fen Tseng, Ladan Fazli, Martin Gleave, Guanghua Xiao, Leah Gandee, Nima Sharifi, Loredana Moro, Tzong Shin Tzai, Jer Tsong Hsieh

研究成果: Article同行評審

32 引文 斯高帕斯(Scopus)

摘要

Altered DAB2IP gene expression often detected in prostate cancer (PCa) is due to epigenetic silencing. In this study, we unveil a new mechanism leading to the loss of DAB2IP protein; an oncogenic S-phase kinase-associated protein-2 (Skp2) as E3 ubiquitin ligase plays a key regulator in DAB2IP degradation. In order to unveil the role of Skp2 in the turnover of DAB2IP protein, both prostate cell lines and prostate cancer specimens with a variety of molecular and cell biologic techniques were employed. We demonstrated that DAB2IP is regulated by Skp2-mediated proteasome degradation in the prostate cell lines. Further analyses identified the N-terminal DAB2IP containing the ubiquitination site. Immunohistochemical study exhibited an inverse correlation between DAB2IP and Skp2 protein expression in the prostate cancer tissue microarray. In contrast, DAB2IP can suppress Skp2 protein expression is mediated through Akt signaling. The reciprocal regulation between DAB2IP and Skp2 can impact on the growth of PCa cells. This reciprocal regulation between DAB2IP and Skp2 protein represents a unique homeostatic balance between tumor suppressor and oncoprotein in normal prostate epithelia, which is apparently altered in cancer cells. The outcome of this study has identified new potential targets for developing new therapeutic strategy for PCa.

原文English
頁(從 - 到)6425-6436
頁數12
期刊Oncotarget
5
發行號15
DOIs
出版狀態Published - 2014

All Science Journal Classification (ASJC) codes

  • 腫瘤科

指紋

深入研究「The role of homeostatic regulation between tumor suppressor DAB2IP and oncogenic Skp2 in prostate cancer growth」主題。共同形成了獨特的指紋。

引用此