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

Authors
 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 
Citation
 MOLECULAR CELL, Vol.37(2) : 183-195, 2010 
Journal Title
 MOLECULAR CELL 
ISSN
 1097-2765 
Issue Date
2010
MeSH
Carcinoma/metabolism* ; Cell Line ; Colonic Neoplasms/metabolism* ; Gene Expression Regulation ; Humans ; Nuclear Receptor Subfamily 1, Group F, Member 1/chemistry ; Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 1/physiology* ; Phosphorylation ; Protein Kinase C-alpha/metabolism* ; Wnt Proteins/metabolism* ; beta Catenin/metabolism*
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 RORalpha-mediated inhibition of canonical Wnt signaling in colon cancer. Wnt5a/PKCalpha-dependent phosphorylation on serine residue 35 of RORalpha is crucial to link RORalpha 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 RORalpha 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 RORalpha, 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.
Full Text
http://www.sciencedirect.com/science/article/pii/S1097276509009526
DOI
10.1016/j.molcel.2009.12.022
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hogeun(김호근)
Lee, Hanna(이한나)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103181
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