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Cell. 2015 Aug 13;162(4):780-94. doi: 10.1016/j.cell.2015.07.013.

Alternative Wnt Signaling Activates YAP/TAZ.

Author information

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.

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.

PMID:
26276632
PMCID:
PMC4538707
DOI:
10.1016/j.cell.2015.07.013
[Indexed for MEDLINE]
Free PMC Article

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