Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation

Journal of Clinical Investigation

Volumn 125, Issue 2, 2015, Pages 687-698

  Sellers, Katherine ^a,b   Fox, Matthew P ^c   Ii, Michael Bousamra ^c,d   Slone, Stephen P ^c   Higashi, Richard M ^a,e   Miller, Donald M ^d   Wang, Yali ^d   Yan, Jun ^d   Yuneva, Mariia O ^b   Deshpande, Rahul ^e   Lane, Andrew N ^a,d,e   Fan, Teresa W M ^a,d,e  

^a UNIVERSITY OF LOUISVILLE   (United States)

^b MEDICAL RESEARCH COUNCIL   (United Kingdom)

^c Department of Surgery ^*  (United States)

^d UNIVERSITY OF LOUISVILLE SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF KENTUCKY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 13; GLUCOSE; GLUTAMINASE; NITROGEN 15; PYRUVATE CARBOXYLASE; GLUTATHIONE; NUCLEOTIDE; TRACER; TUMOR PROTEIN;

ARTICLE; CANCER CELL; CANCER GROWTH; CANCER INHIBITION; CANCER PATIENT; CELL PROLIFERATION; CITRIC ACID CYCLE; COLONY FORMATION; CONTROLLED STUDY; ENZYME ACTIVITY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LIPOGENESIS; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; NUCLEOTIDE METABOLISM; PRIORITY JOURNAL; PROTEIN EXPRESSION; STROMA CELL; ANIMAL; BIOSYNTHESIS; ENZYMOLOGY; FEMALE; GENE EXPRESSION REGULATION; GENETICS; HEK293 CELL LINE; LIPID METABOLISM; LUNG TUMOR; MALE; METABOLISM; PATHOLOGY; RANDOMIZED CONTROLLED TRIAL;

ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; CELL PROLIFERATION; CITRIC ACID CYCLE; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE; GLUTATHIONE; HEK293 CELLS; HUMANS; LIPID METABOLISM; LUNG NEOPLASMS; MALE; MICE; NEOPLASM PROTEINS; NUCLEOTIDES; PYRUVATE CARBOXYLASE; RADIOACTIVE TRACERS;

EID: 84961287801     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI72873     Document Type: Article

References (45)

1. Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309-314.
2. Dang CV, Semenza GL. Oncogenic alterations of metabolism. Trends Biochem Sci. 1999;24(2):68-72.
3. Fan TW, et al. Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes. Mol Cancer. 2008;7:79.
4. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029-1033.
5. Metallo CM, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 2011;481(7381):380-384.
6. Wise DR, et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of a-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci U S A. 2011;108(49):19611-19616.
7. Frezza C, et al. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature. 2011;477(7363):225-228.
8. Mullen AR, et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 2011;481(7381):385-388.
9. Possemato R, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476(7360):346-350.
10. Le A, et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012;15(1):110-121.
11. Yuneva MO, et al. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 2012;15(2):157-170.
12. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
13. Serkova NJ, Spratlin JL, Eckhardt SG. NMRbased metabolomics: Translational application and treatment of cancer. Curr Opin Mol Ther. 2007;9(6):572-585.
14. Lane AN, Fan TWM, Higashi RM. Stable isotope assisted metabolomics in cancer research. IUBMB Life. 2008;60(2):124-129.
15. Guppy M, Leedman P, Zu X, Russell V. Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells. Biochem J. 2002;364(1):309-315.
16. Portais JC, Voisin P, Merle M, Canioni P. Glucose and glutamine metabolism in C6 glioma cells studied by carbon 13 NMR. Biochimie. 1996;78(3):155-164.
17. De Berardinis RJ, et al. Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A. 2007;104(49):19345-19350.
18. Mazurek S, Grimm H, Oehmke M, Weisse G, Teigelkamp S, Eigenbrodt E. Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res. 2000;20(6 D):5151-5154.
19. Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol. 2007;178(1):93-105.
20. Cheng T, et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci U S A. 2011;108(21):8674-8679.
21. Fan TW, et al. Altered regulation of metabolic pathways in human lung cancer discerned by (13) C stable isotope-resolved metabolomics (SIRM). Mol Cancer. 2009;8:41.
22. Marin-Valencia I, et al. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab. 2012;15(6):827-837.
23. Fan TWM, et al. Stable isotope-resolved metabolomic analysis of lithium effects on glial-neuronal metabolism and interactions. Metabolomics. 2010;6(2):165-179.
24. Hertz L, Peng L, Dienel GA. Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab. 2007;27(2):219-249.
25. Warburg O. Versuche an überlebendem Carcinomgewebe (Methoden). Biochem Zeitschr. 1923;142:317-333.
26. Xie H, et al. Targeting lactate dehydrogenase-A (LDH-A) inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor initiating cells. Cell Metab. 2014;19(5):795-809
27. Ochoa-Ruiz E, Diaz-Ruiz R. Anaplerosis in cancer: another step beyond the warburg effect. Am J Mol Biol. 2012;2:291-303.
28. Lane AN, Fan TW, Xie Z, Moseley HN, Higashi RM. Isotopomer analysis of lipid biosynthesis by high resolution mass spectrometry and NMR. Anal Chim Acta. 2009;651(2):201-208.
29. Mazurek S, Eigenbrodt E. The tumor metabolome. Anticancer Res. 2003;23(2 A):1149-1154.
30. Lobo C, Ruiz-Bellido MA, Aledo JC, Marquez J, Nunez De Castro I. Inhibition of glutaminase expression by antisense mRNA decreases growth and tumourigenicity of tumour cells. Biochem J. 2000;348(pt 2):257-261.
31. Seltzer MJ, et al. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010;70(22):8981-8987.
32. Marin-Valencia I, et al. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab. 2012;15(6):827-837.
33. Chandler CS, Ballard FJ. Regulation of the breakdown rates. of biotin-containing proteins in Swiss 3T3-L1 cells. Biochem J. 1988;251(3):749-755.
34. Kim JW, Dang CV. Multifaceted roles of glycolytic enzymes. Trends Biochem Sci. 2005;30(3):142-150.
35. Fan TWM, Lane AN, Higashi RM, eds. The Handbook of Metabolomics. New York, New York, USA: Humana Press; 2012.
36. Lane AN, Fan TW, Bousamra M 2nd, Higashi RM, Yan J, Miller DM. Stable isotope-resolved metabolomics (SIRM) in cancer research with clinical application to nonsmall cell lung cancer. OMICS. 2011;15(3):173-182.
37. Fan TW, Lane AN, Higashi M, Bousamra M 2nd, Kloecker G, Miller DM. Erlotinib-sensitive and resistant lung tumors show radically different metabolic profiles. Exp Molec Pathol. 2009;87:83-86.
38. Bousamra M, Day J, Fan TWM, Kloecker G, Lane AN, Miller DM. Clinical aspects of metabolomics. In: Fan TWM, Higashi RM, Lane AN, eds. The Handbook of Metabolomics. New York, New York, USA: Humana Press; 2012:29-60.
39. Fan TW, Lane AN, Higashi RM, Yan J. Stable isotope resolved metabolomics of lung cancer in a SCID mouse model. Metabolomics. 2011;7(2):257-269.
40. De Graaf RA, Rothman DL, Behar KL. State of the art direct 13C and indirect 1H-[13C] NMR spectroscopy in vivo. A practical guide. NMR Biomed. 2011;24(8):958-972.
41. Maher EA, et al. Metabolism of U-13C glucose in human brain tumors in vivo. NMR Biomed. 2012;25(11):1234-1244.
42. Fan TWM. Metabolomics-edited transcriptomics analysis (Meta). In: McQueen CA ed. Comprehensive Toxicology. 2nd ed. Oxford, United Kingdom: Academic Press; 2010:685-706.
43. Fan TW-M. Sample preparation for metabolomics investigation. In: Fan TW-M, Lane AN, Higashi RM, eds. The Handbook of Metabolomics: Pathway and Flux Analysis, Methods in Pharmacology and Toxicology. New York, New York, USA: Springer Science; 2012:7-27.
44. Rosner B. Fundamentals of Biostatistics. Belmont, California, USA: Thomson; 2006.
45. Lorkiewicz P, Higashi RM, Lane AN, Fan TW. High information throughput analysis of nucleotides and their isotopically enriched isotopologues by direct-infusion FTICR-MS. Metabolomics. 2012;8(5):930-939.