The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer

Several non-hypercalcemic analogs of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D-3) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription factor represses VDR gene expression in human colon cancer cells and blocks the antitumor action of EB1089, a 1,25(OH)(2)D-3 analog, in xenografted mice. In human colon cancers, elevated SNAIL expression correlates with downregulation of VDR.