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All-trans retinoic acid activates E-cadherin expression via promoter hypomethylation in the human colon carcinoma HCT116 cells
- Woo, Young-Ju, Jang, Kyung Lib
- Biochemical and biophysical research communications 2012 v.425 no.4 pp. 944-949
- carcinoma, cell movement, colorectal neoplasms, fibronectins, humans, metastasis, neoplasm cells, retinoic acid, small interfering RNA, vimentin
- 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.