The histone variant H2A.X is a regulator of the epithelial–mesenchymal transition

• Published in: Nature communications Vol. 7; no. 1; p. 10711
• Main Authors: Weyemi, Urbain, Redon, Christophe E., Choudhuri, Rohini, Aziz, Towqir, Maeda, Daisuke, Boufraqech, Myriem, Parekh, Palak R., Sethi, Taresh K., Kasoji, Manjula, Abrams, Natalie, Merchant, Anand, Rajapakse, Vinodh N., Bonner, William M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.02.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 14/1; 14/19; 38/109; 38/15; 38/22; 38/39; 38/61; 38/77; 38/89; 42/41; 631/45/612/100/2286; 631/67/322; 631/80/84/2176; 64/60; 82/29; 82/80; Adenocarcinoma - genetics; Animals; Blotting, Western; Cancer research; Cell Line, Tumor; Colorectal cancer; CRISPR-Cas Systems; Epithelial-Mesenchymal Transition - genetics; Fluorescent Antibody Technique; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genetic Variation; Genomes; HCT116 Cells; HEK293 Cells; Histones - genetics; Homeodomain Proteins - genetics; Humanities and Social Sciences; Humans; Medical research; Metastasis; Mice; Mice, Nude; multidisciplinary; Neoplasm Metastasis - genetics; Neoplasm Transplantation; Real-Time Polymerase Chain Reaction; Science; Science (multidisciplinary); Snail Family Transcription Factors; Transcription factors; Transcription Factors - genetics; Tumors; Zinc Finger E-box-Binding Homeobox 1; United States > US; Maryland
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10711

The epithelial–mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induces mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reverses these changes, as does silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibit a similar metastatic behaviour, but the cells with re-expressed H2A.X are substantially more metastatic. We surmise that H2A.X re-expression leads to partial EMT reversal and increases robustness in the HCT116 cells, permitting them to both form tumours and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlate inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a regulator of EMT. The histone H2A variants are involved in DNA repair, gene regulation and cancer development. In this study, the authors unravel an additional role for H2A.X in the regulation of mesenchymal-like traits and activation of the EMT transcription factors, Slug and ZEB1, in colon cancer cells.