Epigenetic regulation of epithelial-mesenchymal transition by hypoxia in cancer: targets and therapy

Curr Pharm Des. 2015;21(10):1272-8. doi: 10.2174/1381612821666141211145610.


Intratumoral hypoxia followed by stabilization/activation of hypoxia-inducible factor 1 (HIF-1) and its downstream transcriptional factors, is one of the most important mechanisms inducing epithelial-mesenchymal transition (EMT), which has been widely accepted as a crucial step to generate early stage of tumor metastasis. Accumulating evidence suggests that epigenetic mechanisms play important roles in hypoxia-induced EMT and metastasis. These epigenetic regulations are mediated by various players including chromatin modifiers, transcriptional co-regulators, microRNAs, etc. In this review, we discuss how his tone-modifying enzymes and transcriptional co-regulators regulate EMT under hypoxic conditions. Developed or potential anticancer agents targeting epigenetic molecules regulating hypoxia-induced EMT are also discussed.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Cell Hypoxia / physiology
  • Epigenesis, Genetic / physiology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Gene Targeting / trends*
  • Genetic Therapy / trends*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • Signal Transduction / physiology


  • Antineoplastic Agents