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Opposing roles of TGF? and BMP signaling in prostate cancer development.


ABSTRACT: SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor ? (TGF?) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGF? 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 TGF?-BMP signaling and illuminate potential therapeutic targets for prostate cancer.

SUBMITTER: Lu X 

PROVIDER: S-EPMC5795781 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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SMAD4 constrains progression of <i>Pten</i>-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 <i>Pten</i>-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 con  ...[more]

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