Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis

摘要: Genetic aberrations responsible for soft-tissue sarcoma formation in adults are largely unknown, with targeted therapies sorely needed this complex and heterogeneous family of diseases. Here we report that the Hippo pathway is deregulated many sarcomas, resulting elevated expression effector molecule Yes-Associated Protein (YAP). Based on data gathered from human patients, a novel autochthonous mouse model, mechanistic analyses, determined YAP-dependent transcription factor forkhead box M1 (FOXM1) necessary cell proliferation/tumorigenesis subset sarcomas. Notably, FOXM1 directly interacts YAP transcriptional via TEAD1, coregulation numerous critical pro-proliferation targets enhance progression. Finally, pharmacologic inhibition decreases tumor size vivo, making an attractive therapeutic target treatment some subtypes.