Journal of Clinical Investigation’s mouse study shows that inhibiting MCT1 forces cells to switch to glucose energy generation.
Scientists at Universit catholique de Louvain have discovered that although hypoxic tumor cells use glucose to generate energy, well-oxygenated tumor cells use lactate instead. Lactate used as fuel is released from hypoxic tumor cells as a waste product of the chemical reactions that burn glucose, suggesting that these different tumor cells exist in symbiosis. Previously, researchers thought that the tumor cells in these two regions both used glucose to generate energy.
Investigators revealed that well-oxygenated cells took up lactate via the protein monocarboxylate transporter 1 (MCT1), and that inhibiting MCT1 made the well-oxygenated cells switch to using glucose as a fuel to generate energy.
This disrupted the symbiotic relationship between the hypoxic and well-oxygenated tumor cells and led to decreased tumor growth in two mouse models of cancer, as the hypoxic tumor cells became deprived of glucose, and rendered the remaining cells sensitive to irradiation.
Since MCT1 expression was detected exclusively in nonhypoxic regions of human cancer biopsy samples, the researchers suggest that MCT1 is a potential new target for anticancer therapeutics.
The article appeared November 20 in Journal of Clinical Investigation.