Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update

Open Biol. 2017 Sep;7(9):170152. doi: 10.1098/rsob.170152.

Abstract

Cancer cells undergo many different alterations during their transformation, including genetic and epigenetic events. The controlled division of healthy cells can be impaired through the downregulation of tumour suppressor genes. Here, we provide an update of the mechanisms in which epigenetically altered coding and non-coding tumour suppressor genes are implicated. We will highlight the importance of epigenetics in the different molecular pathways that lead to enhanced and unlimited capacity of division, genomic instability, metabolic shift, acquisition of mesenchymal features that lead to metastasis, and tumour plasticity. We will briefly describe these pathways, focusing especially on genes whose epigenetic inactivation through DNA methylation has been recently described, as well as on those that are well established as being epigenetically silenced in cancer. A brief perspective of current clinical therapeutic approaches that can revert epigenetic inactivation of non-coding tumour suppressor genes will also be given.

Keywords: cancer; epigenetics; inactivation; methylation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cell Division
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • DNA Methylation
  • Epigenesis, Genetic* / drug effects
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Genomic Instability
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Promoter Regions, Genetic
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Histones
  • Tumor Suppressor Proteins