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 language | English |
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Article number | 24 |
Journal | Journal of Clinical Medicine |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - 04 02 2016 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2016 by the authors; licensee MDPI, Basel, Switzerland.
Keywords
- 5hmC
- DNA demethylation
- HAP
- Hypoxia
- TET