Tai K.-Y.Shiah S.-G.Shieh Y.-S.Kao Y.-R.Chi C.-Y.Huang E.Lee H.-S.Chang L.-C.PAN-CHYR YANGWu C.-W.2020-12-022020-12-0220070950-9232https://www.scopus.com/inward/record.uri?eid=2-s2.0-34249989097&doi=10.1038%2fsj.onc.1210176&partnerID=40&md5=8c379b7def73f115b0025b490f95a462https://scholars.lib.ntu.edu.tw/handle/123456789/523769Epithelial cell adhesion molecule (Ep-CAM) is believed to have a critical role in carcinogenesis and cell proliferation. However, the association of Ep-CAM with cancer invasion and progression is less clear. We found that Ep-CAM was highly expressed on low-invasive cells compared with highly invasive cells. Forced expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM expression elevated cancer invasiveness. Ep-CAM expression was associated with promoter methylation. Treatment with a demethylating agent, and/or the histone deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and inhibited cancer invasiveness. Using a promoter-reporter construct, we demonstrated methylation of the promoter fragment drive Ep-CAM-silenced transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched for hypermethylated histone 3 lysine 9. When unmethylated and active, this promoter was associated with acetylated histone 3 lysine 9. Furthermore, we observed an increased association of Ep-CAM promoter with repression components as tumor invasiveness increased. In cancer tissues, Ep-CAM expression significantly correlated with tumor progression and associated with promoter methylation. Our data support the idea that modulation of Ep-CAM plays a pivotal role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep-CAM is implicated in enhancing invasive/metastatic proclivity of tumors. ? 2007 Nature Publishing Group All rights reserved.Ep-CAM; Invasion; Promoter methylation[SDGs]SDG3epithelial cell adhesion molecule; histone; histone H3; lysine; acetylation; article; cancer growth; cancer invasion; controlled study; correlation analysis; DNA methylation; female; gene expression; gene repression; gene silencing; genetic transcription; human; human cell; priority journal; promoter region; reporter gene; Antigens, Neoplasm; Blotting, Western; Cell Adhesion Molecules; Cell Line, Tumor; Cell Movement; Disease Progression; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Green Fluorescent Proteins; Histones; Humans; Immunohistochemistry; Luciferases; Lung Neoplasms; Male; Neoplasm Invasiveness; Promoter Regions (Genetics); Protein Processing, Post-Translational; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transfectionjournal article10.1038/sj.onc.1210176172138112-s2.0-34249989097