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

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-dih...

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Main Authors: Alberto Muñoz, Gemma Ferrer-Mayorga, Núria Niell, María Jesús Larriba, Antonio Barbáchano, José Manuel González-Sancho
Format: Article
Language:English
Published: MDPI AG 2013-10-01
Series:Cancers
Subjects:
Wnt
Online Access:http://www.mdpi.com/2072-6694/5/4/1242
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spelling doaj-cc64e6ec95924b64b25c10170c505c402020-11-24T21:07:53ZengMDPI AGCancers2072-66942013-10-01541242126010.3390/cancers5041242Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer CellsAlberto MuñozGemma Ferrer-MayorgaNúria NiellMaría Jesús LarribaAntonio BarbáchanoJosé Manuel González-SanchoThe 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.http://www.mdpi.com/2072-6694/5/4/1242vitamin D1a,25-dihydroxyvitamin D3Wntb-catenincolon cancervitamin D receptor
collection DOAJ
language English
format Article
sources DOAJ
author Alberto Muñoz
Gemma Ferrer-Mayorga
Núria Niell
María Jesús Larriba
Antonio Barbáchano
José Manuel González-Sancho
spellingShingle Alberto Muñoz
Gemma Ferrer-Mayorga
Núria Niell
María Jesús Larriba
Antonio Barbáchano
José Manuel González-Sancho
Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells
Cancers
vitamin D
1a,25-dihydroxyvitamin D3
Wnt
b-catenin
colon cancer
vitamin D receptor
author_facet Alberto Muñoz
Gemma Ferrer-Mayorga
Núria Niell
María Jesús Larriba
Antonio Barbáchano
José Manuel González-Sancho
author_sort Alberto Muñoz
title Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells
title_short Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells
title_full Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells
title_fullStr Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells
title_full_unstemmed Vitamin D Is a Multilevel Repressor of Wnt/b-Catenin Signaling in Cancer Cells
title_sort vitamin d is a multilevel repressor of wnt/b-catenin signaling in cancer cells
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2013-10-01
description 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.
topic vitamin D
1a,25-dihydroxyvitamin D3
Wnt
b-catenin
colon cancer
vitamin D receptor
url http://www.mdpi.com/2072-6694/5/4/1242
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