title: Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells.
abstract: Decreased epithelial cadherin (E-cadherin) gene expression, a hallmark of epithelial-mesenchymal transition (EMT), is essential for triggering metastatic advantage of the colon cancer. Genetic mechanisms underlying the regulation of E-cadherin expression in EMT have been extensively investigated; however, much is unknown about the epigenetic mechanism underlying this process. Here, we identified ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase involved in demethylating di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), as a positive regulator for the expression of E-cadherin in the colon cancer cell line HCT-116. We showed that inactivation of UTX down-regulated E-cadherin gene expression, while overexpression of UTX did the opposite. Notably, overexpression of UTX inhibited migration and invasion of HCT-116 cells. Moreover, UTX demethylated H3K27me3, a histone transcriptional repressive mark, leading to decreased H3K27me3 at the E-cadherin promoter. Further, UTX interacted with the histone acetyltransferase (HAT) protein CBP and recruited it to the E-cadherin promoter, resulting in increased H3K27 acetylation (H3K27ac), a histone transcriptional active mark. UTX positively regulates E-cadherin expression through coordinated regulation of H3K27 demethylation and acetylation, switching the transcriptional repressive state to the transcriptional active state at the E-cadherin promoter. We conclude that UTX may play a role in regulation of E-cadherin gene expression in HCT-116 cells and that UTX may serve as a therapeutic target against the metastasis in the treatment of colon cancer.
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China.|Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zha
authors.affiliation: Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China. lianghoujie@sina.com.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA. bxue@gsu.edu.
authors.forename: Bingzhong
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Biology and Center for Obesity Reversal, Georgia State University, Atlanta, GA, 30303, USA. hshi3@gsu.edu.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D056466:Histone Demethylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D009687:Nuclear Proteins; D056466:Histone Demethylases; C523998:KDM6A protein, human
keywords: Colon cancer; E-cadherin; EMT; H3K27; Histone demethylase; UTX
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