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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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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