(2014) Cancer cell: The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation

Citation

Tremblay AM, Missiaglia E, Galli GG, Hettmer S, Urcia R, Carrara M, Judson RN, Thway K, Nadal G, Selfe JL, Murray G, Calogero RA, De Bari C, Zammit PS, Delorenzi M, Wagers AJ, Shipley J, Wackerhage H, Camargo FD. 2014. The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation. Cancer cell. 26(2):273-87. Pubmed: 25087979 DOI:S1535-6108(14)00230-X

Abstract

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

Related Faculty

Amy Wagers, Ph.D.

Wagers Lab

Amy Wagers seeks to change the way we repair our tissues after an injury. Her research focuses on defining the factors and mechanisms that regulate the migration, expansion, and regenerative potential of adult blood-forming and muscle-forming stem cells.

Fernando Camargo, Ph.D.

Camargo Lab

The Camargo laboratory focuses on the study of adult stem cell biology, organ size regulation, and cancer.