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

Cancers

Mar໚ Jesús Larriba¹  José Manuel González-Sancho¹  Antonio Barbผhano¹  Núria Niell¹  Gemma Ferrer-Mayorga¹ 

[1] Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain;

关键词: vitamin D;    1α;    25-dihydroxyvitamin D₃;    Wnt;    β-catenin;    colon cancer;    vitamin D receptor;   

DOI  :  10.3390/cancers5041242

来源: mdpi

【 摘 要 】

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 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/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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.