转化生长因子β（TGFβ）和骨形态发生蛋白（BMP）信号在前列腺癌发展中的相反作用。
Opposing roles of TGFβ and BMP signaling in prostate cancer development.
作者信息
Lu Xin, Jin Eun-Jung, Cheng Xi, Feng Shan, Shang Xiaoying, Deng Pingna, Jiang Shan, Chang Qing, Rahmy Sharif, Chaudhary Seema, Lu Xuemin, Zhao Ren, Wang Y Alan, DePinho Ronald A
机构信息
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.
出版信息
Genes Dev. 2017 Dec 1;31(23-24):2337-2342. doi: 10.1101/gad.307116.117.
SMAD4 constrains progression of -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 -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 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.
SMAD4抑制p53基因缺失型前列腺癌的进展，并作为转化生长因子β（TGFβ）和骨形态发生蛋白（BMP）信号通路的共同下游节点。在此，我们使用p53基因缺失型前列腺癌模型剖析了TGFβ受体II（TGFBR2）和BMP受体II（BMPR2）的作用。这些研究表明，TGFBR2的分子作用导致了增殖的SMAD4依赖性抑制和凋亡的SMAD4非依赖性激活。相比之下，与单独缺失p53相比，BMPR2缺失延长了生存期，确立了其在BMP6驱动的前列腺癌进展中的促进作用。这些分析揭示了TGFβ-BMP信号传导的复杂性，并阐明了前列腺癌的潜在治疗靶点。
Zotero 插件