Vitamin D Is a Multilevel Repressor of Wnt/β-Catenin Signaling in Cancer Cells

• Published in: Cancers Vol. 5; no. 4; pp. 1242 - 1260
• Main Authors: Larriba, María Jesús, González-Sancho, José Manuel, Barbáchano, Antonio, Niell, Núria, Ferrer-Mayorga, Gemma, Muñoz, Alberto
• Format: Journal Article
• Language: English
• Published: MDPI 21-10-2013
• Subjects: Review
• ISSN: 2072-6694
• DOI: 10.3390/cancers5041242

The 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 D
3
(1,25(OH)
2
D
3
) inhibits Wnt/β-catenin signaling by several mechanisms at different points along the pathway. Additionally, paracrine actions of 1,25(OH)
2
D
3
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)
2
D
3
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/β-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.