Alternative Wnt Signaling Activates YAP/TAZ

作者：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^*

来源：Cell, 2015, 162(4): 780-794.

DOI：10.1016/j.cell.2015.07.013

• PROTEIN-INTERACTION NETWORK
• HIPPO-YAP PATHWAY
• STEM-CELLS
• GASTRULATION
• INHIBITION
• TAZ
• ADIPOGENESIS
• REGENERATION
• MECHANISMS
• FRIZZLED-1

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.

• 出版日期2015-8-13
• 单位复旦大学