8. Reprogramming energy metabolism
Uncontrolled proliferation of malignant cells relies not only on loss of cell cycle control mechanisms but also requires adjustments of cellular energy metabolism.
Under aerobic conditions, oxidative phosphorylation functions as the main metabolic pathway for energy production; cells process glucose, first to pyruvate via glycolysis and thereafter to carbon dioxide in the mitochondria. Under anaerobic conditions, glycolysis is favoured to produce ATP.
Cancer cells can reprogram their glucose metabolism to limit energy production to glycolysis even in the presence of oxygen. This has been termed ‘aerobic glycolysis’. Upregulation of glucose transporters such as GLUT1 is the main mechanism through which aerobic glycolysis is achieved.
This reprogramming of energy metabolism appears paradoxical, as overall energy production from glycolysis is significantly lower (18-fold) than that from oxidative phosphorylation. One explanation for this may be that amplification of glycolysis results in increased production of glycolytic intermediates. These metabolites may then be fed into various biosynthetic pathways, including those that generate the nucleosides and amino acids, which are necessary for the production of new cells. Some cancers have been found to contain two subpopulations of malignant cells that differ in their energy-generating pathways. One subpopulation consists of glucose-dependent cells that secrete lactate, whereas the second preferentially import and utilise the lactate produced by their neighbours as their main energy source, employing part of the citric acid cycle to do so.
9. Tumour-promoting inflammation
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