Abstract
Hypoxia and oncogene expression both stimulate glycolytic metabolism in tumors, thereby leading to lactate production. However, lactate is more than merely a by-product of glycolysis: it can be used as a metabolic fuel by oxidative cancer cells. This phenomenon resembles processes that have been described for skeletal muscle and brain that involve what are known as cell-cell and intracellular lactate shuttles. Two control points regulate lactate shuttles: the lactate dehydrogenase (LDH)-dependent conversion of lactate into pyruvate (and back), and the transport of lactate into and out of cells through specific monocarboxylate transporters (MCTs). In tumors, MCT4 is largely involved in hypoxia-driven lactate release, whereas the uptake of lactate into both tumor cells and tumor endothelial cells occurs via MCT1. Translating knowledge of lactate shuttles to the cancer field offers new perspectives to therapeutically target the hypoxic tumor microenvironment and to tackle tumor angiogenesis.
Footnotes
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FUNDING
This work was supported by the Fonds de la Recherche Scientifique FRS-FNRS; the Fonds de la Recherche Scientifique Médicale; the Télévie; the Belgian Federation Against Cancer; the J. Maisin Foundation; and an Action de Recherche Concertée from the Communauté Française de Belgique [ARC 09/14-020].
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COMPETING INTERESTS
N.D. is a Télévie fellow and O.F. an FRS-FNRS Research Director.
- © 2011. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
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