The Hippo tranducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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The Hippo pathway effector YAP1 controls stem cell fate in epithelial tissues, but its role in stem cells of non-epithelial tissues, such as skeletal muscle, is poorly documented. Here we show that sustained YAP1 activity in mouse activated satellite cells in vivo induces rhabdomyosarcoma (RMS) resembling human embryonal RMS (ERMS) with high penetrance and short latency. The transcriptional program of YAP1 in ERMS drives pro-proliferative pathways whilst decreasing MyoD1 and MEF2 pro-differentiation activity to globally maintain the myoblastic phenotype of ERMS. Normalization of YAP1 expression reduced tumor burden and allowed myogenic differentiation of YAP1-driven and RD ERMS xenografts in situ, thereby identifying YAP1 as a potent RMS-causing oncogene and potential target for differentiation therapy.
提供机构：
University of Torino
创建时间：
2022-02-20
