RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer - PubMed (original) (raw)
. 2010 Jan 29;37(2):183-95.
doi: 10.1016/j.molcel.2009.12.022.
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
Affiliations
- PMID: 20122401
- DOI: 10.1016/j.molcel.2009.12.022
Free article
RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer
Ji Min Lee et al. Mol Cell. 2010.
Free article
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.
Copyright 2010 Elsevier Inc. All rights reserved.
Comment in
- An orphan nuclear receptor finds a home.
Kimmel AR. Kimmel AR. Mol Cell. 2010 Jan 29;37(2):155-7. doi: 10.1016/j.molcel.2010.01.008. Mol Cell. 2010. PMID: 20122397
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