Analyzing and targeting cancer metabolism in vivo

Metabolic reprogramming is a key step in oncogenic transformation including the activation of energy- and anabolic metabolism. Thus, differentiated cells reenter the cell cycle and proliferate. The central metabolism is the ultimate source of energy and building blocks enabling growth and proliferation. Specifically the time resolved analysis of central metabolic pathways allows an insight in metabolic dynamics and allows the comparison and even quantification of pathway usage (Liu et al. 2012). Glucose and glutamine were identified as the major fuel sources for cancer cells. Thus, glycolysis and glutaminolysis are central metabolic pathways that may possess molecular targets for an effective metabolic treatment of cancer cells not only in vitro but also in vivo. However, until now the activity of glutaminolysis in vivo is still under debate. Although a high glutaminolytic activity can be observed in cell cultures the in vivo-activity of this pathway has rarely been shown. To better characterize the metabolic activity of hepatocellular carcinoma (HCC) we studied a mouse model for HCC by analyzing the metabolome, proteome and usage of glucose and glutamine by 13C stable isotope labeling in vivo. The data show that in vivo-metabolism is strongly transformed (metabolic reprogramming) and characterized by altered usage of glucose and glutamine. Further analyses and integration of the multilevel data may allow identifying molecular targets within central metabolism. Liu L. et al. (2012) Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature 483(7391):608-12