Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer.
Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.
|Year of Publication||
2016 Mar 08
|PubMed Central ID||
T32 GM007287 / GM / NIGMS NIH HHS / United States
R01 CA168653 / CA / NCI NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
P30CA1405141 / CA / NCI NIH HHS / United States
R01CA168653 / CA / NCI NIH HHS / United States
T32GM007287 / GM / NIGMS NIH HHS / United States
K08 HL119355 / HL / NHLBI NIH HHS / United States
T32GM007753 / GM / NIGMS NIH HHS / United States
K08HL119355 / HL / NHLBI NIH HHS / United States