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Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes

1
Research Center for Tumor Medical Science and Graduate Institute of Cancer Biology, China Medical University, Taichung 40402, Taiwan
2
Institute of Clinical Medicine, China Medical University, Taichung 40402, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editors: David A. Brenner, Tatiana Kisseleva and Jonas Fuxe
J. Clin. Med. 2016, 5(2), 24; https://doi.org/10.3390/jcm5020024
Received: 29 November 2015 / Revised: 15 January 2016 / Accepted: 26 January 2016 / Published: 4 February 2016
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition)
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-1α transcriptional regulation to modulate HIF-1α 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. View Full-Text
Keywords: TET; 5hmC; DNA demethylation; hypoxia; HAP TET; 5hmC; DNA demethylation; hypoxia; HAP
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MDPI and ACS Style

Kao, S.-H.; Wu, K.-J.; Lee, W.-H. Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes. J. Clin. Med. 2016, 5, 24.

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