Vitamin D and colon cancer: Gene regulation and interplay with Wnt signalling and SNAIL1

• Published in: Anticancer research Vol. 28; no. 3A; p. 1621
• Main Authors: Munoz, A, Ordonez-Moran, P, Larriba, MJ, Pendas-Franco, N, Aguilera, O, Gonzalez-Sancho, J M
• Format: Journal Article
• Language: English
• Published: 01.06.2008
• ISSN: 0250-7005

Previously we demonstrated that 1,25(OH) sub(2)D sub(3) induces Ecadherin and promotes differentiation of human colon cancer cells. In addition, 1,25(OH) sub(2)D sub(3) antagonizes the Wnt/ beta e-catenin signalling, which is aberrantly activated in most human colon cancers, a) by increasing the amount of VDR bound to beta -catenin, thus reducing the formation of beta eta-catenin/TCF4 complexes and their transcriptional activity, and b) by inducing the nuclear export of beta -catenin. Also, we reported that the transcription factor SNAIL1, an inducer of epithelial-to-mesenchymal transition (EMT), represses VDR expression and blocks 1,25(OH) sub(2)D sub(3) effects in cultured cells and xenografted mice, and that over-expression of SNAIL1 in colon tumours correlates with down-regulation of VDR and may so be responsible for the loss of responsiveness to treatments with 1,25(OH) sub(2)D sub(3) or its analogs.