Dysregulated glycolysis as an oncogenic event

Abstract

Enhanced glycolysis in cancer, called the Warburg effect, is a well-known feature of cancer metabolism. Recent advances revealed that the Warburg effect is coupled to many other cancer properties, including adaptation to hypoxia and low nutrients, immortalisation, resistance to oxidative stress and apoptotic stimuli, and elevated biomass synthesis. These linkages are mediated by various oncogenic molecules and signals, such as c-Myc, p53, and the insulin/Ras pathway. Furthermore, several regulators of glycolysis have been recently identified as oncogene candidates, including the hypoxia-inducible factor pathway, sirtuins, adenosine monophosphate-activated kinase, glycolytic pyruvate kinase M2, phosphoglycerate mutase, and oncometabolites. The interplay between glycolysis and oncogenic events will be the focus of this review.

Fig. 1

Network of transcriptional and posttranscriptional regulation of glycolysis relevant to tumourigenesis. Classical oncogenic factors are indicated by green circles, while other signalling molecules are shown in blue. HIF-1 is indicated in red, and the metabolic sensor AMPK and sirtuins are shown in orange. The arrow indicates a positive effect, while the others are inhibitory effects. Pathways branching from glycolysis are described in the grey box, and some essential metabolites are in purple. See the text for additional mechanistic details and abbreviation definitions