Alternative Wnt Signaling Activates YAP/TAZ

Cell. 2015 Aug 13;162(4):780-94. doi: 10.1016/j.cell.2015.07.013.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Proteins
  • Cell Line
  • Frizzled Receptors / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Phosphoproteins / metabolism*
  • Trans-Activators
  • Transcription Factors
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Frizzled Receptors
  • Fzd1 protein, mouse
  • Phosphoproteins
  • Trans-Activators
  • Transcription Factors
  • Wwtr1 protein, mouse
  • YAP1 (Yes-associated) protein, human
  • Yap1 protein, mouse
  • beta Catenin

Associated data

  • GEO/GSE70506