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Vitamin D is a multilevel repressor of Wnt/β-catenin signaling in cancer cells

AuthorsLarriba, María Jesús ; González-Sancho, José Manuel ; Barbáchano, Antonio ; Niell, Núria ; Ferrer-Mayorga, Gemma ; Muñoz Terol, Alberto
KeywordsVitamin D
1α,25-dihydroxyvitamin D3
Colon cancer
Vitamin D receptor
Issue Date2013
PublisherMultidisciplinary Digital Publishing Institute
CitationCancers 5(4): 1242-1260 (2013)
AbstractThe Wnt/β-catenin signaling pathway is abnormally activated in most colorectal cancers and in a proportion of other neoplasias. This activation initiates or contributes to carcinogenesis by regulating the expression of a large number of genes in tumor cells. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits Wnt/β-catenin signaling by several mechanisms at different points along the pathway. Additionally, paracrine actions of 1,25(OH)2D3 on stromal cells may also repress this pathway in neighbouring tumor cells. Here we review the molecular basis for the various mechanisms by which 1,25(OH)2D3 antagonizes Wnt/β-catenin signaling, preferentially in human colon carcinoma cells, and the consequences of this inhibition for the phenotype and proliferation rate. The effect of the vitamin D system on Wnt/beta-catenin signaling and tumor growth in animal models will also be commented in detail. Finally, we revise existing data on the relation between vitamin D receptor expression and vitamin D status and the expression of Wnt/β-catenin pathway genes and targets in cancer patients.
DescriptionThis article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license.
Publisher version (URL)http://dx.doi.org/10.3390/cancers5041242
Appears in Collections:(IIBM) Artículos
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