Vitamin D and the Epithelial to Mesenchymal Transition

Abstract

Several studies support reciprocal regulation between the active vitamin D derivative 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and the epithelial to mesenchymal transition (EMT). Thus, 1,25(OH)2D3 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)2D3 action by repressing the transcription of VDR gene encoding the high affinity vitamin D receptor that mediates 1,25(OH)2D3 effects. Consequently, the balance between the strength of 1,25(OH)2D3 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)2D3 and EMT.

Figure 1

Scheme showing the mechanisms involved in the reciprocal regulation between 1,25(OH)₂D₃ and EMT in human colon cancer cells. Proteins and pathways displayed in blue are associated with an epithelial phenotype, while those shown in red are related with a mesenchymal phenotype. Blue and red lines are used to indicate induction or repression, respectively.