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Alternative Wnt Signaling Activates YAP/TAZ
- Park, Hyun Woo;
- Kim, Young Chul;
- Yu, Bo;
- Moroishi, Toshiro;
- Mo, Jung-Soon;
- Plouffe, Steven W;
- Meng, Zhipeng;
- Lin, Kimberly C;
- Yu, Fa-Xing;
- Alexander, Caroline M;
- Wang, Cun-Yu;
- Guan, Kun-Liang
Published Web Location
https://doi.org/10.1016/j.cell.2015.07.013Abstract
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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