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Differential molecular mechanistic behavior of HDACs in cancer progression

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Abstract

Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs’ role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review.

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Acknowledgements

Thanks to Dr. Paramdeep Singh for contributing to the preparation of manuscript. Special thanks to Dr. Sandeep Singh and Prof. Anjana Munshi for critically revising and editing the manuscript.

Funding

Council of Scientific and Industrial Research (CSIR), New Delhi, is acknowledged for Senior Research Fellowship (SRF) to Tashvinder Singh and Prabhsimran Kaur for Ph.D. Declarations. DST-FIST grant (SR/FST/LS-I/2017/49) to Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab is acknowledged with thanks.

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  1. Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India

    Tashvinder Singh, Prabhsimran Kaur, Sandeep Singh & Anjana Munshi

  2. Department of Radiology, AIIMS, Bathinda, 151001, India

    Paramdeep Singh

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  1. Tashvinder Singh
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The idea of the article was framed by TS, SS and AM. Literature was searched by TS, SS and AM and data analysis was done by TS, PK, PS, SS and AM. The draft was jointly prepared by TS and PK. It was critically revised by PS, SS and AM.

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Correspondence to Sandeep Singh or Anjana Munshi.

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Singh, T., Kaur, P., Singh, P. et al. Differential molecular mechanistic behavior of HDACs in cancer progression. Med Oncol 39, 171 (2022). https://doi.org/10.1007/s12032-022-01770-4

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