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Vitamin D Effects on Cell Differentiation and Stemness in Cancer

Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz, and CIBERONC, Arturo Duperier 4, 28029 Madrid, Spain
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Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2413; https://doi.org/10.3390/cancers12092413
Received: 31 July 2020 / Revised: 21 August 2020 / Accepted: 22 August 2020 / Published: 25 August 2020
(This article belongs to the Special Issue Stemness and Differentiation in Cancer)
Vitamin D3 is the precursor of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), a pleiotropic hormone that is a major regulator of the human genome. 1,25(OH)2D3 modulates the phenotype and physiology of many cell types by controlling the expression of hundreds of genes in a tissue- and cell-specific fashion. Vitamin D deficiency is common among cancer patients and numerous studies have reported that 1,25(OH)2D3 promotes the differentiation of a wide panel of cultured carcinoma cells, frequently associated with a reduction in cell proliferation and survival. A major mechanism of this action is inhibition of the epithelial–mesenchymal transition, which in turn is largely based on antagonism of the Wnt/β-catenin, TGF-β and EGF signaling pathways. In addition, 1,25(OH)2D3 controls the gene expression profile and phenotype of cancer-associated fibroblasts (CAFs), which are important players in the tumorigenic process. Moreover, recent data suggest a regulatory role of 1,25(OH)2D3 in the biology of normal and cancer stem cells (CSCs). Here, we revise the current knowledge of the molecular and genetic basis of the regulation by 1,25(OH)2D3 of the differentiation and stemness of human carcinoma cells, CAFs and CSCs. These effects support a homeostatic non-cytotoxic anticancer action of 1,25(OH)2D3 based on reprogramming of the phenotype of several cell types. View Full-Text
Keywords: vitamin D; cell differentiation; stemness; cancer; carcinoma cells; cancer-associated fibroblasts; cancer stem cells; organoids; epithelial-mesenchymal transition; Wnt/β-catenin vitamin D; cell differentiation; stemness; cancer; carcinoma cells; cancer-associated fibroblasts; cancer stem cells; organoids; epithelial-mesenchymal transition; Wnt/β-catenin
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MDPI and ACS Style

Fernández-Barral, A.; Bustamante-Madrid, P.; Ferrer-Mayorga, G.; Barbáchano, A.; Larriba, M.J.; Muñoz, A. Vitamin D Effects on Cell Differentiation and Stemness in Cancer. Cancers 2020, 12, 2413. https://doi.org/10.3390/cancers12092413

AMA Style

Fernández-Barral A, Bustamante-Madrid P, Ferrer-Mayorga G, Barbáchano A, Larriba MJ, Muñoz A. Vitamin D Effects on Cell Differentiation and Stemness in Cancer. Cancers. 2020; 12(9):2413. https://doi.org/10.3390/cancers12092413

Chicago/Turabian Style

Fernández-Barral, Asunción, Pilar Bustamante-Madrid, Gemma Ferrer-Mayorga, Antonio Barbáchano, María Jesús Larriba, and Alberto Muñoz. 2020. "Vitamin D Effects on Cell Differentiation and Stemness in Cancer" Cancers 12, no. 9: 2413. https://doi.org/10.3390/cancers12092413

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