Fernández-Barral Asunción, Bustamante-Madrid Pilar, Ferrer-Mayorga Gemma, Barbáchano Antonio, Larriba María Jesús, Muñoz Alberto
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.
Cancers (Basel). 2020 Aug 25;12(9):2413. doi: 10.3390/cancers12092413.
Vitamin D is the precursor of 1α,25-dihydroxyvitamin D (1,25(OH)D), a pleiotropic hormone that is a major regulator of the human genome. 1,25(OH)D 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)D 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)D 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)D 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)D 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)D based on reprogramming of the phenotype of several cell types.
维生素D是1α,25-二羟基维生素D（1,25(OH)D）的前体，1,25(OH)D是一种多效激素，是人类基因组的主要调节因子。1,25(OH)D通过以组织和细胞特异性方式控制数百个基因的表达，调节多种细胞类型的表型和生理功能。维生素D缺乏在癌症患者中很常见，许多研究报告称，1,25(OH)D可促进多种培养的癌细胞分化，这通常与细胞增殖和存活的减少有关。这种作用的主要机制是抑制上皮-间质转化，而这又主要基于对Wnt/β-连环蛋白、TGF-β和EGF信号通路的拮抗作用。此外，1,25(OH)D控制癌症相关成纤维细胞（CAF）的基因表达谱和表型，CAF是肿瘤发生过程中的重要参与者。此外，最近的数据表明1,25(OH)D在正常和癌症干细胞（CSC）生物学中具有调节作用。在此，我们回顾了目前关于1,25(OH)D对人癌细胞、CAF和CSC的分化和干性调节的分子和遗传基础的知识。这些效应支持了1,25(OH)D基于对几种细胞类型表型重编程的稳态非细胞毒性抗癌作用。
