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

Research output: Contribution to journalArticlepeer-review

312 Citations (Scopus)

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

Bibliographical note

Funding Information:
We thank the following colleagues for generously sharing the following materials: Dr. Duojia Pan for YAP transgenic mice, Dr. Ben Ho Park for PIK3CA mutation knockin MCF10A cells, Dr. Yingzi Yang for Gna11 −/− Gnaq f/f and Gna12 −/− Gna13 f/f MEFs, Dr. Dae-Sik Lim for Lats1 −/− Lats2 f/f MEFs, Dr. Xi He for FZD1, FZD2, and FZD5 plasmids, and Dr. Liguang Chen for ROR1 plasmids. We also thank Dr. Karl Willert for the helpful discussion. This work was supported by grants from the NIH (EY022611, CA132809, and DE015964) to K.-L.G. and Cellular and Molecular Pharmacology training grant (T32 GM007752) to S.W.P.

Publisher Copyright:
© 2015 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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