Vitamin D-3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling

Citation
Hg. Palmer et al., Vitamin D-3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling, J CELL BIOL, 154(2), 2001, pp. 369-387
Citations number
92
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
2
Year of publication
2001
Pages
369 - 387
Database
ISI
SICI code
0021-9525(20010723)154:2<369:VDPTDO>2.0.ZU;2-A
Abstract
The beta -catenin signaling pathway is deregulated in nearly all colon canc ers. Nonhypercalcemic vitamin D3 (1 alpha ,25-dehydroxyvitamin D-3) analogu es are candidate drugs to treat this neoplasia. We show that these compound s promote the differentiation of human colon carcinoma SW480 cells expressi ng vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subli ne (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1 alpha ,2 5(OH)(2)D-3 induced the expression of E-cadherin and other adhesion protein s (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the tran slocation of beta -catenin, plakoglobin, and ZO-1 from the nucleus to the p lasma membrane. Ligand-activated VDR competed with T cell transcription fac tor (TCF)-4 for beta -catenin binding. Accordingly, 1 alpha ,25(OH)(2)D-3 r epressed beta -catenin-TCF-4 transcriptional activity. Moreover, VDR activi ty was enhanced by ectopic beta -catenin and reduced by TCF-4. Also, 1 alph a ,25(OH)(2)D-3 inhibited expression of beta -catenin-TCF-4-responsive gene s, c-myc, peroxisome proliferator-activated receptor delta, Tcf-1, and CD44 , whereas it induced expression of ZO-1. Our results show that lot,25(OH)2D 3 induces E-cadherin and modulates beta -catenin-TCF-4 target genes in a ma nner opposite to that of beta -catenin, promoting the differentiation of co lon carcinoma cells.