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

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-lik...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756313/
https://www.ncbi.nlm.nih.gov/pubmed/26876487
http://dx.doi.org/10.1038/ncomms10711
Descripción
Sumario: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.