Vitamin D and colon cancer: Gene regulation and interplay with Wnt signalling and SNAIL1
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 amo...
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Published in | Anticancer research Vol. 28; no. 3A; p. 1621 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
01.06.2008
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Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 0250-7005 |