All-trans retinoic acid activates E-cadherin expression via promoter hypomethylation in the human colon carcinoma HCT116 cells.
All-trans retinoic acid (ATRA) inhibits the invasive and metastatic potentials of various cancer cells; however, the underlying mechanism is unclear. Here, we show that ATRA activated E-cadherin expression via promoter hypomethylation to facilitate Sp1 binding on its recognition sites in human colon carcinoma HCT116 cells. This effect was mediated by retinoic acid receptor-β2, as demonstrated by knock-down experiments using a specific siRNA. As a result, ATRA increased cell-to-cell interactions, reduced cell migration, and downregulated levels of Vimentin and Fibronectin in HCT116 cells. The present study thus provides the mechanism for the beneficial effects of ATRA in the treatment of metastatic human carcinomas.
Department of Microbiology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Young-Ju
YJ
Woo
Kyung Lib
KL
Jang
D015820:Cadherins / Q000235:genetics*; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D015820:Cadherins; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin