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

被引：165

作者：

Lee, Ji Min ^{[2
]}

Kim, Ik Soo ^{[2
]}

Kim, Hyunkyung ^{[2
]}

Lee, Jason S. ^{[2
]}

Kim, Kyeongkyu ^{[2
]}

Yim, Hwa Young ^{[1
]}

Jeong, Jiyeong ^{[1
]}

Kim, Jung Hwa ^{[3
]}

Kim, Ji-Young ^{[4
]}

Lee, Hanna ^{[5
]}

Seo, Sang-Beom ^{[4
]}

Kim, Hogeun ^{[5
]}

Rosenfeld, Michael G. ^{[6
,7
]}

Kim, Keun Il ^{[1
]}

Baek, Sung Hee ^{[2
]}

机构：

[1] Sookmyung Womens Univ, Dept Biol Sci, Seoul 140742, South Korea

[2] Seoul Natl Univ, Dept Biol Sci, Creat Res Initiat Ctr Chromatin Dynam, Seoul 151742, South Korea

[3] Inha Univ, Dept Med Sci, Inchon 402751, South Korea

[4] Chung Ang Univ, Dept Life Sci, Seoul 156756, South Korea

[5] Yonsei Univ, Dept Pathol, Coll Med, Seoul 120749, South Korea

[6] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

来源：

MOLECULAR CELL | 2010年 / 37卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

BETA-CATENIN; AXIS FORMATION; PATHWAY; WNT-5A; CELLS; GENE;

D O I：

10.1016/j.molcel.2009.12.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：183 / 195

页数：13

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