RORα Attenuates Wnt/β-Catenin Signaling by PKCα-Dependent Phosphorylation in Colon Cancer

Ji Min Lee, Ik Soo Kim, Hyunkyung Kim, Jason S. Lee, Kyeongkyu Kim, Hwa Young Yim, Jiyeong Jeong, Jung Hwa Kim, Ji Young Kim, Hanna Lee, Sang Beom Seo, Hogeun Kim, Michael G. Rosenfeld, Keun Il Kim, Sung Hee Baek

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)183-195
Number of pages13
JournalMolecular Cell
Volume37
Issue number2
DOIs
Publication statusPublished - 2010 Jan 29
Externally publishedYes

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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