学术报告：The Role of COUP-TFII in Prostate Tumor Growth and Metastasis
报告人：   Sophia Y. Tsai, Ph.D.
                  Professor, Department of Molecular and Cellular Biology, Baylor College of Medicine
主持人：   冯新华  教授
时   间：   2012年11月13日（星期二）下午2点
地   点：   医学院综合楼205报告厅

Absract：
The prevalence of PTEN loss and fusion of TMPRSS2 with ETS family members in prostate cancer patients implicate signaling cascades endowed by these two factors play critical role in prostate tumorigenesis. However, the precise mechanism underlying the functional cooperation between PTEN and ETS transcription factors and how PTEN indolent tumors acquire metastatic potential remain largely undefined. Here we show that COUP-TFII, a member of nuclear receptor superfamily, serves as the central player linking PTEN, ETS transcription factor and TGF-b signaling to promote prostate cancer progression and metastasis. Inactivation of PTEN elevates the phosphorylation of oncogenic ERG/ETV-1 to coordinately induce COUP-TFII expression, and COUP-TFII potentiates PTEN null indolent tumor to become a metastatic-prone cancer. Mechanistically, COUP-TFII is shown to mediate PTEN induced tumor growth and more importantly to overcome the TGF-b-dependent growth barrier through direct interaction with Smad4 to inhibit its transcription activity. In prostate cancer patients, COUP-TFII is associated with disease progression and might serve an independent prognostic factor for recurrence. Together, our findings uncover a central signaling pathway from PTEN/ETS/COUP-TFII to TGF-b, which is critical for prostate tumorigenesis.