Alternative Wnt Signaling Activates YAP/TAZ.

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Abstract

The transcriptional co-activators YAP and TAZ are key regulators of organ size and tissue homeostasis, and their dysregulation contributes to human cancer. Here, we discover YAP/TAZ as bona fide downstream effectors of the alternative Wnt signaling pathway. Wnt5a/b and Wnt3a induce YAP/TAZ activation independent of canonical Wnt/β-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis" that consists of Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2 to promote YAP/TAZ activation and TEAD-mediated transcription. YAP/TAZ mediate the biological functions of alternative Wnt signaling, including gene expression, osteogenic differentiation, cell migration, and antagonism of Wnt/β-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling.

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Journal

Journal ID (iso-abbrev): Cell

Title: Cell

ISSN (Electronic): 1097-4172

ISSN (Print): 0092-8674

Publication date (Electronic): Aug 13 2015

Volume: 162

Issue: 4

Affiliations

[1 ] Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.

[2 ] Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Department of Cardiology, Veterans Medical Research Foundation, San Diego, CA 92161, USA.

[3 ] Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

[4 ] Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

[5 ] McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI 53706, USA.

[6 ] Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: kuguan@ucsd.edu.

Article

Publisher Item ID: S0092-8674(15)00850-8 Mid ID: NIHMS708990

DOI: 10.1016/j.cell.2015.07.013

PubMed ID: 26276632

SO-VID: d01886ce-f681-42ae-aaba-999b95cd7116

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