Alternative Wnt Signaling Activates YAP/TAZ

Hyun Woo Park, Young Chul Kim, Bo Yu, Toshiro Moroishi, Jung Soon Mo, Steven W. Plouffe, Zhipeng Meng, Kimberly C. Lin, Fa Xing Yu, Caroline M. Alexander, Cun Yu Wang, Kun Liang Guan

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Abstract

Summary 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.

Original languageEnglish
Article number8328
Pages (from-to)780-794
Number of pages15
JournalCell
Volume162
Issue number4
DOIs
Publication statusPublished - 2015 Aug 17

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Park, H. W., Kim, Y. C., Yu, B., Moroishi, T., Mo, J. S., Plouffe, S. W., Meng, Z., Lin, K. C., Yu, F. X., Alexander, C. M., Wang, C. Y., & Guan, K. L. (2015). Alternative Wnt Signaling Activates YAP/TAZ. Cell, 162(4), 780-794. [8328]. https://doi.org/10.1016/j.cell.2015.07.013