RNAi screens in mice identify physiological regulators of oncogenic growth.
作者： Brice E. Keyes , Naoki Oshimori , Elaine Fuchs , Slobodan Beronja , Peter Janki
DOI: 10.1038/NATURE12464
关键词:
摘要: Tissue growth is the multifaceted outcome of a cell's intrinsic capabilities and its interactions with surrounding environment. Decoding these complexities essential for understanding human development tumorigenesis. Here we tackle this problem by carrying out first genome-wide RNA-interference-mediated screens in mice. Focusing on skin oncogenic (Hras(G12V)-induced) hyperplasia, our uncover previously unknown as well anticipated regulators embryonic epidermal growth. Among top screen hits are Mllt6 Wnt effector β-catenin, which maintain Hras(G12V)-dependent hyperproliferation. We also expose β-catenin an unanticipated antagonist normal growth, functioning through Wnt-independent intercellular adhesion. Finally, validate functional significance mouse cancers, thereby establishing feasibility vivo mammalian investigations to dissect tissue By documenting some regulators, pave way future other raise promise unearthing new targets cancer therapies.
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