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Cancers 2013, 5(4), 1242-1260; doi:10.3390/cancers5041242

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

Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain
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Received: 20 August 2013 / Revised: 2 October 2013 / Accepted: 10 October 2013 / Published: 21 October 2013
(This article belongs to the Special Issue Vitamin D: Role in Cancer Causation, Progression and Therapy)
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Abstract

The Wnt/b-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 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits Wnt/b-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/b-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/b-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/b-catenin pathway genes and targets in cancer patients.
Keywords: vitamin D; 1a,25-dihydroxyvitamin D3; Wnt; b-catenin; colon cancer; vitamin D receptor vitamin D; 1a,25-dihydroxyvitamin D3; Wnt; b-catenin; colon cancer; vitamin D receptor
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Larriba, M.J.; González-Sancho, J.M.; Barbáchano, A.; Niell, N.; Ferrer-Mayorga, G.; Muñoz, A. Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells. Cancers 2013, 5, 1242-1260.

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