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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5361| Title: | Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling |
| Keywords: | Vitamin D Vitamin D receptor β-catenin E-cadherin Colon cancer |
| Publisher: | Rockefeller University Press |
| Description: | et al. The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1α,25(OH)2D3 induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the translocation of β-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. Accordingly, 1α,25(OH)2D3 repressed β-catenin–TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic β-catenin and reduced by TCF-4. Also, 1α,25(OH)2D3 inhibited expression of β-catenin–TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor δ, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1α,25(OH)2D3 induces E-cadherin and modulates β-catenin–TCF-4 target genes in a manner opposite to that of β-catenin, promoting the differentiation of colon carcinoma cells. H.G. Pálmer and J.M. González-Sancho were recipients of fellowships from the Comunidad Autónoma de Madrid. This work was supported by a grant from the Plan Nacional de Investigación y Desarrollo (SAF98-0060), Ministerio de Ciencia y Tecnología of Spain. Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5361 |
| Other Identifiers: | Journal of Cell Biology 154(2): 369–388 (2001) 0021-9525 http://hdl.handle.net/10261/5361 10.1083/jcb.200102028 |
| Appears in Collections: | Digital Csic |
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