Opposing roles of TGFβ and BMP signaling in prostate cancer development

SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor beta (TGF beta) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGF beta 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 itspromoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity ofTGF beta-BMPsignaling and illuminate potential therapeutic targets for prostate cancer.