The Hippo Transducer YAP1 Transforms Activated Satellite Cells and Is a Potent Effector of Embryonal Rhabdomyosarcoma Formation

摘要: The role of the Hippo pathway effector YAP1 in soft tissue sarcomas is poorly defined. Here we report that activity elevated human embryonal rhabdomyosarcoma (ERMS). In mice, sustained hyperactivity activated, but not quiescent, satellite cells induces ERMS with high penetrance and short latency. Via its transcriptional program TEAD1, directly regulates several major hallmarks ERMS. YAP1-TEAD1 upregulate pro-proliferative oncogenic genes maintain differentiation block by interfering MYOD1 MEF2 pro-differentiation activities. Normalization expression reduces tumor burden xenografts allows YAP1-driven to differentiate in situ. Collectively, our results identify as a potent driver promising target for therapy.