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RORα Attenuates Wnt/β-Catenin Signaling by PKCα-Dependent Phosphorylation in Colon Cancer
- Source :
-
Molecular Cell . Jan2010, Vol. 37 Issue 2, p183-195. 13p. - Publication Year :
- 2010
-
Abstract
- Summary: Wnt family members play diverse roles in development and disease. Noncanonical Wnt ligands can inhibit canonical Wnt signaling depending on the cellular context; however, the underlying mechanism of this antagonism remains poorly understood. Here we identify a specific mechanism of orphan nuclear receptor RORα-mediated inhibition of canonical Wnt signaling in colon cancer. Wnt5a/PKCα-dependent phosphorylation on serine residue 35 of RORα is crucial to link RORα to Wnt/β-catenin signaling, which exerts inhibitory function of the expression of Wnt/β-catenin target genes. Intriguingly, there is a significant correlation of reduction of RORα phosphorylation in colorectal tumor cases compared to their normal counterpart, providing the clinical relevance of the findings. Our data provide evidence for a role of RORα, functioning at the crossroads between the canonical and the noncanonical Wnt signaling pathways, in mediating transrepression of the Wnt/β-catenin target genes, thereby providing new approaches for the development of therapeutic agents for human cancers. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 37
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 47827911
- Full Text :
- https://doi.org/10.1016/j.molcel.2009.12.022