Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer

Cancer Cell

Volumn 24, Issue 2, 2013, Pages 213-228

  Patra, KrushnaC ^a   Wang, Qi ^a   Bhaskar, PrashanthT ^a   Miller, Luke ^a   Wang, Zebin ^a   Wheaton, Will ^b   Chandel, Navdeep ^b   Laakso, Markku ^c   Muller, WilliamJ ^d   Allen, EricL ^e   Jha, AbhishekK ^e   Smolen, GromoslawA ^e   Clasquin, MichelleF ^e   Robey, R Brooks ^f,g   Hay, Nissim ^a,h  

^a UNIVERSITY OF ILLINOIS   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

^c UNIVERSITY OF EASTERN FINLAND   (Finland)

^d MCGILL UNIVERSITY   (Canada)

^e AGIOS PHARMACEUTICALS   (United States)

^f VA MEDICAL CENTER   (United States)

^g DARTMOUTH MEDICAL SCHOOL   (United States)

^h JESSE BROWN VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE CITRATE LYASE; ASPARTATE AMINOTRANSFERASE; HEXOKINASE; HEXOKINASE 1; HEXOKINASE 2; PHOSPHOGLYCERATE DEHYDROGENASE; RIBONUCLEOTIDE; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; CANCER SURVIVAL; CARBON BALANCE; CARBON UTILIZATION; CARBOXYLATION; CARCINOGENESIS; CARCINOGENICITY; CITRIC ACID CYCLE; CONTROLLED STUDY; DECARBOXYLATION; FATTY ACID SYNTHESIS; GENE DELETION; GLUCOSE HOMEOSTASIS; GLUCOSE INTAKE; GLUCOSE TOLERANCE; GLUCOSE UTILIZATION; GLYCOSYLATION; IN VITRO STUDY; IN VIVO STUDY; LIPID DIET; LIPOGENESIS; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; NUCLEOTIDE METABOLISM; PENTOSE PHOSPHATE CYCLE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR VOLUME;

MUS;

EID: 84881557242     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2013.06.014     Document Type: Article

References (36)

1. Cheong H., Lu C., Lindsten T., Thompson C.B. Therapeutic targets in cancer cell metabolism and autophagy. Nat. Biotechnol. 2012, 30:671-678.
2. DeBerardinis R.J., Mancuso A., Daikhin E., Nissim I., Yudkoff M., Wehrli S., Thompson C.B. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. USA 2007, 104:19345-19350.
3. Felig P., Wahren J. Fuel homeostasis in exercise. N.Engl. J. Med. 1975, 293:1078-1084.
4. Fueger P.T., Heikkinen S., Bracy D.P., Malabanan C.M., Pencek R.R., Laakso M., Wasserman D.H. Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice. Am. J. Physiol. Endocrinol. Metab. 2003, 285:E958-E963.
5. Gaglio D., Metallo C.M., Gameiro P.A., Hiller K., Danna L.S., Balestrieri C., Alberghina L., Stephanopoulos G., Chiaradonna F. Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol. Syst. Biol. 2011, 7:523.
6. Gottlob K., Majewski N., Kennedy S., Kandel E., Robey R.B., Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 2001, 15:1406-1418.
7. Heikkinen S., Pietilä M., Halmekytö M., Suppola S., Pirinen E., Deeb S.S., Jänne J., Laakso M. Hexokinase II-deficient mice: prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes. J.Biol. Chem. 1999, 274:22517-22523.
8. Jackson E.L., Willis N., Mercer K., Bronson R.T., Crowley D., Montoya R., Jacks T., Tuveson D.A. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 2001, 15:3243-3248.
9. Johnson L., Mercer K., Greenbaum D., Bronson R.T., Crowley D., Tuveson D.A., Jacks T. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 2001, 410:1111-1116.
10. Kalhan S.C., Hanson R.W. Resurgence of serine: an often neglected but indispensable amino Acid. J.Biol. Chem. 2012, 287:19786-19791.
11. Kaplan O., Navon G., Lyon R.C., Faustino P.J., Straka E.J., Cohen J.S. Effects of 2-deoxyglucose on drug-sensitive and drug-resistant human breast cancer cells: toxicity and magnetic resonance spectroscopy studies of metabolism. Cancer Res. 1990, 50:544-551.
12. Komurov K., Tseng J.T., Muller M., Seviour E.G., Moss T.J., Yang L., Nagrath D., Ram P.T. The glucose-deprivation network counteracts lapatinib-induced toxicity in resistant ErbB2-positive breast cancer cells. Mol. Syst. Biol. 2012, 8:596.
13. Lee W.N., Boros L.G., Puigjaner J., Bassilian S., Lim S., Cascante M. Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2-13C2]glucose. Am. J. Physiol. 1998, 274:E843-E851.
14. Locasale J.W., Cantley L.C. Genetic selection for enhanced serine metabolism in cancer development. Cell Cycle 2011, 10:3812-3813.
15. Lunt S.Y., Vander Heiden M.G. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 2011, 27:441-464.
16. Lyon R.C., Cohen J.S., Faustino P.J., Megnin F., Myers C.E. Glucose metabolism in drug-sensitive and drug-resistant human breast cancer cells monitored by magnetic resonance spectroscopy. Cancer Res. 1988, 48:870-877.
17. Majewski N., Nogueira V., Bhaskar P., Coy P.E., Skeen J.E., Gottlob K., Chandel N.S., Thompson C.B., Robey R.B., Hay N. Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol. Cell 2004, 16:819-830.
18. Mathupala S.P., Rempel A., Pedersen P.L. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J.Biol. Chem. 2001, 276:43407-43412.
19. Muller W.J., Sinn E., Pattengale P.K., Wallace R., Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 1988, 54:105-115.
20. Owen O.E., Kalhan S.C., Hanson R.W. The key role of anaplerosis and cataplerosis for citric acid cycle function. J.Biol. Chem. 2002, 277:30409-30412.
21. Palmieri D., Fitzgerald D., Shreeve S.M., Hua E., Bronder J.L., Weil R.J., Davis S., Stark A.M., Merino M.J., Kurek R., et al. Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis. Mol. Cancer Res. 2009, 7:1438-1445.
22. Possemato R., Marks K.M., Shaul Y.D., Pacold M.E., Kim D., Birsoy K., Sethumadhavan S., Woo H.K., Jang H.G., Jha A.K., et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011, 476:346-350.
23. Ranger J.J., Levy D.E., Shahalizadeh S., Hallett M., Muller W.J. Identification of a Stat3-dependent transcription regulatory network involved in metastatic progression. Cancer Res. 2009, 69:6823-6830.
24. Robey R.B., Hay N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 2006, 25:4683-4696.
25. Robey R.B., Hay N. Is Akt the "Warburg kinase"? Akt-energy metabolism interactions and oncogenesis. Semin. Cancer Biol. 2009, 19:25-31.
26. Ruzankina Y., Pinzon-Guzman C., Asare A., Ong T., Pontano L., Cotsarelis G., Zediak V.P., Velez M., Bhandoola A., Brown E.J. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 2007, 1:113-126.
27. Schulze A., Harris A.L. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 2012, 491:364-373.
28. Shedden K., Taylor J.M., Enkemann S.A., Tsao M.S., Yeatman T.J., Gerald W.L., Eschrich S., Jurisica I., Giordano T.J., Misek D.E., et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat. Med. 2008, 14:822-827. Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.
29. Shinohara Y., Yamamoto K., Kogure K., Ichihara J., Terada H. Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines. Cancer Lett. 1994, 82:27-32.
30. Ursini-Siegel J., Hardy W.R., Zuo D., Lam S.H., Sanguin-Gendreau V., Cardiff R.D., Pawson T., Muller W.J. ShcA signalling is essential for tumour progression in mouse models of human breast cancer. EMBO J. 2008, 27:910-920.
31. van de Vijver M.J., He Y.D., van't Veer L.J., Dai H., Hart A.A., Voskuil D.W., Schreiber G.J., Peterse J.L., Roberts C., Marton M.J., et al. A gene-expression signature as a predictor of survival in breast cancer. N.Engl. J. Med. 2002, 347:1999-2009.
32. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033.
33. Wilson J.E. Hexokinases. Rev. Physiol. Biochem. Pharmacol. 1995, 126:65-198.
34. Wilson J.E. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J.Exp. Biol. 2003, 206:2049-2057.
35. Wolf A., Agnihotri S., Micallef J., Mukherjee J., Sabha N., Cairns R., Hawkins C., Guha A. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J.Exp. Med. 2011, 208:313-326.
36. Ying H., Kimmelman A.C., Lyssiotis C.A., Hua S., Chu G.C., Fletcher-Sananikone E., Locasale J.W., Son J., Zhang H., Coloff J.L., et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012, 149:656-670.