Functional characterization and imaging of oxidative lactate metabolism in cancer
(2017)
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- Authors
- Supervisors
- Sonveaux, Pierre
- Abstract
- Increasing evidence indicate that lactate, the end-product of a glycolytic metabolism, promotes tumor progression. In addition to being used as an oxidative fuel, lactate indeed stimulates angiogenesis by activating transcription factors HIF-1 in oxidative cancer cells and endothelial cells, and NF-kB in endothelial cells. Our work shows that lactate does not activate NF-kB in oxidative cancer cells, because NADH produced during its oxidation is used in mitochondria rather than fueling NAP(P)H oxidases. Thus, lactate influx inhibition can prevent the oxidative use of lactate in cancer. A main target is inward monocarboxylate transporter 1 (MCT1). We therefore developed a tracer of lactate for positron emission tomography that allows to predict and to document a response to MCT1 inhibitors in vivo. Together, our work contributes to a better understanding and therapeutic exploitation of lactate transport in cancer.
- Affiliations
Citations
Van Hee, V. (2017). Functional characterization and imaging of oxidative lactate metabolism in cancer. https://hdl.handle.net/2078.5/181930