SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity of TGFβ-BMP signaling and illuminate potential therapeutic targets for prostate cancer.
Genes & development. 2017 Dec 01 [Epub]
Xin Lu, Eun-Jung Jin, Xi Cheng, Shan Feng, Xiaoying Shang, Pingna Deng, Shan Jiang, Qing Chang, Sharif Rahmy, Seema Chaudhary, Xuemin Lu, Ren Zhao, Y Alan Wang, Ronald A DePinho
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA., Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, Indiana 46556, USA., Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA., Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.