Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer

A. E. Witt, C. W. Lee, T. I. Lee, D. J. Azzam, B. Wang, C. Caslini, F. Petrocca, J. Grosso, M. Jones, E. B. Cohick, A. B. Gropper, C. Wahlestedt, A. L. Richardson, R. Shiekhattar, R. A. Young, T. A. Ince

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.

Original languageEnglish (US)
Pages (from-to)1707-1720
Number of pages14
JournalOncogene
Volume36
Issue number12
DOIs
StatePublished - Mar 23 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Witt, A. E., Lee, C. W., Lee, T. I., Azzam, D. J., Wang, B., Caslini, C., Petrocca, F., Grosso, J., Jones, M., Cohick, E. B., Gropper, A. B., Wahlestedt, C., Richardson, A. L., Shiekhattar, R., Young, R. A., & Ince, T. A. (2017). Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer. Oncogene, 36(12), 1707-1720. https://doi.org/10.1038/onc.2016.337