[HTML][HTML] β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis

J Rosenbluh, D Nijhawan, AG Cox, X Li, JT Neal… - Cell, 2012 - cell.com
J Rosenbluh, D Nijhawan, AG Cox, X Li, JT Neal, EJ Schafer, TI Zack, X Wang, A Tsherniak
Cell, 2012cell.com
Wnt/β-catenin signaling plays a key role in the pathogenesis of colon and other cancers;
emerging evidence indicates that oncogenic β-catenin regulates several biological
processes essential for cancer initiation and progression. To decipher the role of β-catenin
in transformation, we classified β-catenin activity in 85 cancer cell lines in which we
performed genome-scale loss-of-function screens and found that β-catenin active cancers
are dependent on a signaling pathway involving the transcriptional regulator YAP1 …
Summary
Wnt/β-catenin signaling plays a key role in the pathogenesis of colon and other cancers; emerging evidence indicates that oncogenic β-catenin regulates several biological processes essential for cancer initiation and progression. To decipher the role of β-catenin in transformation, we classified β-catenin activity in 85 cancer cell lines in which we performed genome-scale loss-of-function screens and found that β-catenin active cancers are dependent on a signaling pathway involving the transcriptional regulator YAP1. Specifically, we found that YAP1 and the transcription factor TBX5 form a complex with β-catenin. Phosphorylation of YAP1 by the tyrosine kinase YES1 leads to localization of this complex to the promoters of antiapoptotic genes, including BCL2L1 and BIRC5. A small-molecule inhibitor of YES1 impeded the proliferation of β-catenin-dependent cancers in both cell lines and animal models. These observations define a β-catenin-YAP1-TBX5 complex essential to the transformation and survival of β-catenin-driven cancers.
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