Environment impacts the metabolic dependencies of ras-driven non-small cell lung cancer

Shawn M. Davidson, Thales Papagiannakopoulos, Benjamin A. Olenchock, Julia E. Heyman, Mark A. Keibler, Alba Luengo, Matthew R. Bauer, Abhishek K. Jha, James P. O'Brien, Kerry A. Pierce, Dan Y. Gui, Lucas B. Sullivan, Thomas M. Wasylenko, Lakshmipriya Subbaraj, Christopher R. Chin, Gregory Stephanopolous, Bryan T. Mott, Tyler Jacks, Clary B. Clish, Matthew G. Van Der Heiden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

524 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)517-528
Number of pages12
JournalCell Metabolism
Issue number3
StatePublished - Mar 8 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Physiology
  • Cell Biology


Dive into the research topics of 'Environment impacts the metabolic dependencies of ras-driven non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this