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

Author

Listed:
  • Urbain Weyemi

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Christophe E. Redon

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Rohini Choudhuri

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Towqir Aziz

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Daisuke Maeda

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Myriem Boufraqech

    (Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Palak R. Parekh

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Taresh K. Sethi

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • Manjula Kasoji

    (Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute)

  • Natalie Abrams

    (Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute)

  • Anand Merchant

    (Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute)

  • Vinodh N. Rajapakse

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

  • William M. Bonner

    (Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health)

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.

Suggested Citation

  • Urbain Weyemi & Christophe E. Redon & Rohini Choudhuri & Towqir Aziz & Daisuke Maeda & Myriem Boufraqech & Palak R. Parekh & Taresh K. Sethi & Manjula Kasoji & Natalie Abrams & Anand Merchant & Vinodh, 2016. "The histone variant H2A.X is a regulator of the epithelial–mesenchymal transition," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10711
    DOI: 10.1038/ncomms10711
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