Alternative Wnt Signaling Activates YAP/TAZ

摘要

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/beta-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis'' that consists of Wnt-FZD/ROR-Ga alpha(12/13)-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/beta-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling.