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

Author(s): Weyemi U,  Redon CE,  Choudhuri R,  Aziz T,  Maeda D,  Boufraqech M,  Parekh PR,  Sethi TK,  Kasoji M,  Abrams N,  Merchant A,  Rajapakse VN,  Bonner WM

Journal: Nat Commun

Date: 2016 Feb 15

Major Program(s) or Research Group(s): CBRG

PubMed ID: 26876487

PMC ID: PMC4756313

Abstract: 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.