Journal article

beta-Catenin-Driven Cancers Require a YAP1 Transcriptional Complex for Survival and Tumorigenesis

Joseph Rosenbluh, Deepak Nijhawan, Andrew G Cox, Xingnan Li, James T Neal, Eric J Schafer, Travis I Zack, Xiaoxing Wang, Aviad Tsherniak, Anna C Schinzel, Diane D Shao, Steven E Schumacher, Barbara A Weir, Francisca Vazquez, Glenn S Cowley, David E Root, Jill P Mesirov, Rameen Beroukhim, Calvin J Kuo, Wolfram Goessling Show all

Cell | CELL PRESS | Published : 2012

Abstract

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 th..

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University of Melbourne Researchers

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Awarded by SPORE career development award


Awarded by NIH


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

We thank the members of the Hahn lab for helpful discussions and L. Gafney and L. Solomon for assistance with graphic arts. This work was supported in part by NIH/NCI grants R01 CA140545 (W.C.H.), RC2 CA148268 (W.C.H.), U54 CA143798 (R.B.), U01 DK085527 (C.J.K.), U01 CA151920 (C.J.K.), R01 DK085720 (C.J.K.), U54 CA112962 (A.T., J.P.M., and W.C.H.), R01 DK090311 (W.G.), the Pew Charitable Trust (W.G.), a Fidelity Foundation grant (C.J.K.), a Stanford University Dean's Fellowship (J.T.N.), a DoD breast cancer postdoctoral fellowship W81XWH-10-1-0062 (X.W.), Conquer Cancer Foundation Young Investigator Award and Sass Foundation Fellowship (D.N.), a SPORE career development award P50 CA127003 (J.R.), and an NIH F32 postdoctoral fellowship F32 GM090437 (J.R.). J.R. is a John Svenson postdoctoral fellow. W.C.H. and R.B. are consultants for Novartis Pharmaceuticals.