期刊
CELL METABOLISM
卷 15, 期 1, 页码 110-121出版社
CELL PRESS
DOI: 10.1016/j.cmet.2011.12.009
关键词
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资金
- The Sol Goldman Pancreatic Cancer Research fund
- Leukemia Lymphoma Society [LLS-6363-11]
- Stand-Up-to-Cancer/American Association for Cancer Research translational
- University of Louisville CTSPGP [20044, 20061]
- National Institutes of Health National Center for Research Resources (NIH NCRR) [5P20RR018733]
- Kentucky Challenge for Excellence
- Brown Foundation
- Kentucky Lung Cancer Research Program
- National Science Foundation [EPS-0447479]
- [1R21NS074151-01]
- [5R01CA051497-21]
- [5R01CA057341-20]
- [1R01CA118434-01A2]
- [3R01CA118434-02S1]
Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrientpoor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using stable isotope-resolved metabolomics. Using [U-C-13]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-C-13,N-15]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, and glutamine contributed significantly to citrate carbons. Under glucose deprivation, glutamine-derived fumarate, malate, and citrate were significantly increased. Their C-13-labeling patterns demonstrate an alternative energy-generating glutaminolysis pathway involving a glucose-independent TCA cycle. The essential role of glutamine metabolism in cell survival and proliferation under hypoxia and glucose deficiency makes them susceptible to the glutaminase inhibitor BPTES and hence could be targeted for cancer therapy.
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