Vitamin D and the Epithelial to Mesenchymal Transition

Several studies support reciprocal regulation between the active vitamin D derivative 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and the epithelial to mesenchymal transition (EMT). Thus, 1,25(OH)(2)D(3) inhibits EMT via the induction of a variety of target genes that encode cell adhesion and polarity proteins responsible for the epithelial phenotype and through the repression of key EMT inducers. Both direct and indirect regulatory mechanisms mediate these effects. Conversely, certain master EMT inducers inhibit 1,25(OH)(2)D(3) action by repressing the transcription of VDR gene encoding the high affinity vitamin D receptor that mediates 1,25(OH)(2)D(3) effects. Consequently, the balance between the strength of 1,25(OH)(2)D(3) signaling and the induction of EMT defines the cellular phenotype in each context. Here we review the current understanding of the genes and mechanisms involved in the interplay between 1,25(OH)(2)D(3) and EMT.