Metabolism of cancer
Tumor cells commonly exhibit aerobic glycolysis, or the “Warburg effect,” a metabolic transformation that allows cells to undergo enhanced proliferation without significant respiration, despite the presence of oxygen. While the origins of this effect are still not completely understood, it is directly connected with tumorigenesis through mutation or differential expression of several metabolic enzymes. As such, e latter play an active role in tumorigenesis. As a resulT, metabolism is now emerging as a potential therapeutic target in cancer. To effectively target cancer cell metabolism, a complete understanding of the metabolic pathways preferentially used by tumor cells is required. In particular, efforts must be made to accurately quantify metabolic flux in cancer cells, as fluxes represent the definitive function of enzymes. In order to address this problem we develop effective tools for estimating fluxes and confidence intervals in various biological systems using isotope tracers and mass spectrometry. These tools include metabolic flux analysis (MFA) and non-targeted tracer fate detection (NTFD). Applied to cancer cells, we quantify how substrates such as glucose and glutamine are metabolized in the TCA cycle, glycolysis, lipogenesis and other pathways to support tumor cell growth. By studying changes in metabolic fluxes that occur as a function of oncogene and tumor suppressor expression we hope to understand how metabolism enables cancer cells to grow and survive.