Hypoxia, epithelial-mesenchymal transition, and tet-mediated epigenetic changes

Shih Han Kao, Kou Juey Wu*, Wen Hwa Lee

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

Abstract

Tumor hypoxia is a pathophysiologic outcome of disrupted microcirculation with inadequate supply of oxygen, leading to enhanced proliferation, epithelial-mesenchymal transition (EMT), metastasis, and chemo-resistance. Epigenetic changes induced by hypoxia are well documented, and they lead to tumor progression. Recent advances show that DNA demethylation mediated by the Ten-eleven translocation (TET) proteins induces major epigenetic changes and controls key steps of cancer development. TET enzymes serve as 5mC (5-methylcytosine)-specific dioxygenases and cause DNA demethylation. Hypoxia activates the expression of TET1, which also serves as a co-activator of HIF-1a transcriptional regulation to modulate HIF-1a downstream target genes and promote epithelial-mesenchymal transition. As HIF is a negative prognostic factor for tumor progression, hypoxia-activated prodrugs (HAPs) may provide a favorable therapeutic approach to lessen hypoxia-induced malignancy.

Original languageEnglish
Article number24
JournalJournal of Clinical Medicine
Volume5
Issue number2
DOIs
StatePublished - 04 02 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

  • 5hmC
  • DNA demethylation
  • HAP
  • Hypoxia
  • TET

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