Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer

Cell Metab. 2016 Mar 8;23(3):517-28. doi: 10.1016/j.cmet.2016.01.007. Epub 2016 Feb 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood Glucose
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Glucose / metabolism
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mitochondria / metabolism
  • Mutation, Missense
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Pyruvic Acid / metabolism
  • Tumor Microenvironment*


  • Blood Glucose
  • KRAS protein, human
  • Pyruvic Acid
  • Proto-Oncogene Proteins p21(ras)
  • Glucose