biostudies-literatureUnknown119(8)Alvarez-Diaz SThe active vitamin D metabolite 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] has wide but not fully understood antitumor activity. A previous transcriptomic analysis of 1alpha,25(OH)2D3 action on human colon cancer cells revealed cystatin D (CST5), which encodes an inhibitor of several cysteine proteases of the cathepsin family, as a candidate target gene. Here we report that 1alpha,25(OH)2D3 induced vitamin D receptor (VDR) binding to, and activation of, the CST5 promoter and increased CST5 RNA and protein levels in human colon cancer cells. In cells lacking endogenous cystatin D, ectopic cystatin D expression inhibited both proliferation in vitro and xenograft tumor growth in vivo. Furthermore, cystatin D inhibited migration and anchorage-independent growth, antagonized the Wnt/beta-The Journal of clinical investigation2343-58https://www.ebi.ac.uk/biostudies/studies/S-EPMC2719930biostudies-literatureCystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells.PMC2719930Astudillo AAlvarez-Diaz SGarcia JMValle NFreije JMBonilla FLopez-Otin CQuesada VMunoz APena CfalseCystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells.The active vitamin D metabolite 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] has wide but not fully understood antitumor activity. A previous transcriptomic analysis of 1alpha,25(OH)2D3 action on human colon cancer cells revealed cystatin D (CST5), which encodes an inhibitor of several cysteine proteases of the cathepsin family, as a candidate target gene. Here we report that 1alpha,25(OH)2D3 induced vitamin D receptor (VDR) binding to, and activation of, the CST5 promoter and increased CST5 RNA and protein levels in human colon cancer cells. In cells lacking endogenous cystatin D, ectopic cystatin D expression inhibited both proliferation in vitro and xenograft tumor growth in vivo. Furthermore, cystatin D inhibited migration and anchorage-independent growth, antagonized the Wnt/beta-2009-01-01T00:00:00Z2009 Aug2025-04-19T05:36:19.484Z2019-03-27T00:23:56ZS-EPMC27199301966268310.1172/jci37205