Abstract #SY18-3: Cancer cell addiction to glutamine

Oncogenes that control metabolism. Craig B. Thompson, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104 Proliferating cancer cells exhibit a robust but seemingly wasteful metabolism. Two nutrients, glucose and glutamine, are consumed by tumor cells at rates in vast excess of their utilization by vegetative cells. The uptake of each of these nutrients is under the control of distinct oncogenes. The primary signaling pathway that directs glucose uptake and metabolism is initiated by PI3K and inhibited by PTEN. In contrast, glutaminolysis is controlled by oncogenic levels of myc. Glutamine and glucose metabolism facilitate distinct mitocondrially-dependent synthetic reactions required for growth. Recent evidence suggests tumor suppressors are counter-regulators of mitochondrial biosynthesis. In the case of hypoxia, conversion to anaerobic glycolysis is induced by activation of HIF-1\#945;. In the case of glucose limitation, conversion to fatty acid oxidation is mediated by activation of p53. How these oncogenes and tumor suppressors collaborate in the regulation of metabolic pathways will be discussed.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr SY18-3.