Rho GTPase activity modulates Wnt3a/beta-catenin signaling.

Journal Article (Journal Article)

Wnt proteins constitute a family of secreted signaling molecules that regulate highly conserved pathways essential for development and, when aberrantly activated, drive oncogenesis in a number of human cancers. A key feature of the most widely studied Wnt signaling cascade is the stabilization of cytosolic beta-catenin, resulting in beta-catenin nuclear translocation and transcriptional activation of multiple target genes. In addition to this canonical, beta-catenin-dependent pathway, Wnt3A has also been shown to stimulate RhoA GTPase. While the importance of activated Rho to non-canonical Wnt signaling is well appreciated, the potential contribution of Wnt3A-stimulated RhoA to canonical beta-catenin-dependent transcription has not been examined and is the focus of this study. We find that activated Rho is required for Wnt3A-stimulated osteoblastic differentiation in C3H10T1/2 mesenchymal stem cells, a biological phenomenon mediated by stabilized beta-catenin. Using expression microarrays and real-time RT-PCR analysis, we show that Wnt3A-stimulated transcription of a subset of target genes is Rho-dependent, indicating that full induction of these Wnt targets requires both beta-catenin and Rho activation. Significantly, neither beta-catenin stabilization nor nuclear translocation stimulated by Wnt3A is affected by inhibition or activation of RhoA. These findings identify Rho activation as a critical element of the canonical Wnt3A-stimulated, beta-catenin-dependent transcriptional program.

Full Text

Duke Authors

Cited Authors

  • Rossol-Allison, J; Stemmle, LN; Swenson-Fields, KI; Kelly, P; Fields, PE; McCall, SJ; Casey, PJ; Fields, TA

Published Date

  • November 2009

Published In

Volume / Issue

  • 21 / 11

Start / End Page

  • 1559 - 1568

PubMed ID

  • 19482078

Pubmed Central ID

  • PMC2735600

Electronic International Standard Serial Number (EISSN)

  • 1873-3913

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2009.05.010


  • eng

Conference Location

  • England