title: Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer.
abstract: 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.
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
authors: Shawn M
authors: SM
authors: Davidson
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Thales
authors: T
authors: Papagiannakopoulos
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Benjamin A
authors: BA
authors: Olenchock
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Julia E
authors: JE
authors: Heyman
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Mark A
authors: MA
authors: Keibler
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Alba
authors: A
authors: Luengo
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Matthew R
authors: MR
authors: Bauer
authors: Elucidata Corporation, Cambridge, MA 02139, USA.
authors: Abhishek K
authors: AK
authors: Jha
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: James P
authors: JP
authors: O'Brien
authors: Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
authors: Kerry A
authors: KA
authors: Pierce
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Dan Y
authors: DY
authors: Gui
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Lucas B
authors: LB
authors: Sullivan
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Thomas M
authors: TM
authors: Wasylenko
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Lakshmipriya
authors: L
authors: Subbaraj
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Christopher R
authors: CR
authors: Chin
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Gregory
authors: G
authors: Stephanopolous
authors: National Center for Advancing Translational Sciences, NIH, Bethesda, MD 20892, USA.
authors: Bryan T
authors: BT
authors: Mott
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Tyler
authors: T
authors: Jacks
authors: Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
authors: Clary B
authors: CB
authors: Clish
authors: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: mvh@mit.edu.
authors: Matthew G
authors: MG
authors: Vander Heiden
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D020125:Mutation, Missense; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D019289:Pyruvic Acid / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D001786:Blood Glucose; C117307:KRAS protein, human; D019289:Pyruvic Acid; D016283:Proto-Oncogene Proteins p21(ras); D005947:Glucose