Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments
Open Access
- 1 November 2011
- journal article
- review article
- Published by The Company of Biologists in Disease Models & Mechanisms
- Vol. 4 (6), 727-732
- https://doi.org/10.1242/dmm.007724
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.Keywords
This publication has 51 references indexed in Scilit:
- Regulation of cancer cell metabolismNature Reviews Cancer, 2011
- Challenges in Pharmacotherapy of Neoplastic Diseases – The Search for AddictionsFrontiers in Pharmacology, 2010
- Tumor Metabolism of Lactate: The Influence and Therapeutic Potential for MCT and CD147 RegulationFuture Oncology, 2009
- Cell–cell and intracellular lactate shuttlesThe Journal of Physiology, 2009
- Computational analyses of mammalian lactate dehydrogenases: Human, mouse, opossum and platypus LDHsComputational Biology and Chemistry, 2009
- Blood Lactate is an Important Energy Source for the Human BrainJournal of Cerebral Blood Flow & Metabolism, 2009
- Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in miceJCI Insight, 2008
- Laser microdissection expression profiling of marginal edges of colorectal tumours reveals evidence of increased lactate metabolism in the aggressive phenotypeGut, 2008
- Negligible direct lactate oxidation in subsarcolemmal and intermyofibrillar mitochondria obtained from red and white rat skeletal muscleThe Journal of Physiology, 2007
- Issues concerning the construction of a metabolic model for neuronal activationJournal of Neuroscience Research, 2003