ROR alpha Attenuates Wnt/beta-Catenin Signaling by PKC alpha-Dependent Phosphorylation in Colon Cancer
- Authors
- Lee, Ji Min; Kim, Ik Soo; Kim, Hyunkyung; Lee, Jason S.; Kim, Kyeongkyu; Yim, Hwa Young; Jeong, Jiyeong; Kim, Jung Hwa; Kim, Ji-Young; Lee, Hanna; Seo, Sang-Beom; Kim, Hogeun; Rosenfeld, Michael G.; Kim, Keun Il; Baek, Sung Hee
- Issue Date
- Jan-2010
- Publisher
- CELL PRESS
- Keywords
- HUMDISEASE; SIGNALING
- Citation
- MOLECULAR CELL, v.37, no.2, pp 183 - 195
- Pages
- 13
- Journal Title
- MOLECULAR CELL
- Volume
- 37
- Number
- 2
- Start Page
- 183
- End Page
- 195
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13286
- DOI
- 10.1016/j.molcel.2009.12.022
- ISSN
- 1097-2765
1097-4164
- 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 ROR alpha-mediated inhibition of canonical Wnt signaling in colon cancer. Wnt5a/PKC alpha-dependent phosphorylation on serine residue 35 of ROR alpha is crucial to link ROR alpha to Wnt/beta-catenin signaling, which exerts inhibitory function of the expression of Wnt/beta-catenin target genes. Intriguingly, there is a significant correlation of reduction of ROR alpha 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 ROR alpha, functioning at the crossroads between the canonical and the noncanonical Wnt signaling pathways, in mediating transrepression of the Wnt/beta-catenin target genes, thereby providing new approaches for the development of therapeutic agents for human cancers.
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