Journal
ONCOTARGET
Volume 7, Issue 12, Pages 15200-15214Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7710
Keywords
hypoxia; hypoxia-inducible factors; hypotaurine; metabolomics; glioma
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Funding
- National Natural Science Foundation of China [81372695, 81472374, 21435006, 81272788, 81402061]
- National Natural Science Foundation of China (Creative Research Group Project) [21321064]
- Ministry of Science and Technology of China [2012AA01A305, 2012CB721002]
- Intramural Research Program at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH)
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Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.
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