KEGG   PATHWAY: mmu05230
Entry
mmu05230                    Pathway                                
Name
Central carbon metabolism in cancer - Mus musculus (house mouse)
Description
Malignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. He showed that cancer cells consume a large amount of glucose, maintain high rate of glycolysis and convert a majority of glucose into lactic acid even under normal oxygen concentrations (Warburg's Effects). More recently, it has been recognized that the 'Warburg effect' encompasses a similarly increased utilization of glutamine. From the intermediate molecules provided by enhanced glycolysis and glutaminolysis, cancer cells synthesize most of the macromolecules required for the duplication of their biomass and genome. These cancer-specific alterations represent a major consequence of genetic mutations and the ensuing changes of signalling pathways in cancer cells. Three transcription factors, c-MYC, HIF-1 and p53, are key regulators and coordinate regulation of cancer metabolism in different ways, and many other oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53.
Class
Human Diseases; Cancer: overview
Pathway map
mmu05230  Central carbon metabolism in cancer
mmu05230

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
20525  Slc2a1; solute carrier family 2 (facilitated glucose transporter), member 1 [KO:K07299]
20526  Slc2a2; solute carrier family 2 (facilitated glucose transporter), member 2 [KO:K07593]
103988  Gck; glucokinase [KO:K12407] [EC:2.7.1.2]
18746  Pkm; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
18597  Pdha1; pyruvate dehydrogenase E1 alpha 1 [KO:K00161] [EC:1.2.4.1]
18598  Pdha2; pyruvate dehydrogenase E1 alpha 2 [KO:K00161] [EC:1.2.4.1]
68263  Pdhb; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
228026  Pdk1; pyruvate dehydrogenase kinase, isoenzyme 1 [KO:K12077] [EC:2.7.11.2]
22059  Trp53; transformation related protein 53 [KO:K04451]
100126824  Sco2; SCO2 cytochrome c oxidase assembly protein [KO:K23755]
20514  Slc1a5; solute carrier family 1 (neutral amino acid transporter), member 5 [KO:K05616]
64384  Sirt3; sirtuin 3 [KO:K11413] [EC:2.3.1.286]
80879  Slc16a3; solute carrier family 16 (monocarboxylic acid transporters), member 3 [KO:K08180]
50721  Sirt6; sirtuin 6 [KO:K11416] [EC:2.3.1.286]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
15251  Hif1a; hypoxia inducible factor 1, alpha subunit [KO:K08268]
16590  Kit; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
17295  Met; met proto-oncogene [KO:K05099] [EC:2.7.10.1]
19713  Ret; ret proto-oncogene [KO:K05126] [EC:2.7.10.1]
13649  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
13866  Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
18211  Ntrk1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
18213  Ntrk3; neurotrophic tyrosine kinase, receptor, type 3 [KO:K05101] [EC:2.7.10.1]
18595  Pdgfra; platelet derived growth factor receptor, alpha polypeptide [KO:K04363] [EC:2.7.10.1]
18596  Pdgfrb; platelet derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]
14182  Fgfr1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
14183  Fgfr2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
14184  Fgfr3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
14255  Flt3; FMS-like tyrosine kinase 3 [KO:K05092] [EC:2.7.10.1]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
216456  Gls2; glutaminase 2 (liver, mitochondrial) [KO:K01425] [EC:3.5.1.2]
14660  Gls; glutaminase [KO:K01425] [EC:3.5.1.2]
14380  G6pd2; glucose-6-phosphate dehydrogenase 2 [KO:K00036] [EC:1.1.1.49 1.1.1.363]
14381  G6pdx; glucose-6-phosphate dehydrogenase X-linked [KO:K00036] [EC:1.1.1.49 1.1.1.363]
15277  Hk2; hexokinase 2 [KO:K00844] [EC:2.7.1.1]
212032  Hk3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
15275  Hk1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
216019  Hkdc1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
18641  Pfkl; phosphofructokinase, liver, B-type [KO:K00850] [EC:2.7.1.11]
18642  Pfkm; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
56421  Pfkp; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
18648  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
56012  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
16828  Ldha; lactate dehydrogenase A [KO:K00016] [EC:1.1.1.27]
16832  Ldhb; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
16833  Ldhc; lactate dehydrogenase C [KO:K00016] [EC:1.1.1.27]
106557  Ldhal6b; lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
15926  Idh1; isocitrate dehydrogenase 1 (NADP+), soluble [KO:K00031] [EC:1.1.1.42]
269951  Idh2; isocitrate dehydrogenase 2 (NADP+), mitochondrial [KO:K00031] [EC:1.1.1.42]
319801  Tigar; Trp53 induced glycolysis regulatory phosphatase [KO:K14634] [EC:3.1.3.46]
19211  Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
56717  Mtor; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
20539  Slc7a5; solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 [KO:K13780]
Compound
C00022  Pyruvate
C00024  Acetyl-CoA
C00025  L-Glutamate
C00026  2-Oxoglutarate
C00031  D-Glucose
C00036  Oxaloacetate
C00037  Glycine
C00041  L-Alanine
C00042  Succinate
C00049  L-Aspartate
C00062  L-Arginine
C00064  L-Glutamine
C00065  L-Serine
C00073  L-Methionine
C00074  Phosphoenolpyruvate
C00078  L-Tryptophan
C00079  L-Phenylalanine
C00082  L-Tyrosine
C00085  D-Fructose 6-phosphate
C00092  D-Glucose 6-phosphate
C00097  L-Cysteine
C00122  Fumarate
C00123  L-Leucine
C00135  L-Histidine
C00148  L-Proline
C00149  (S)-Malate
C00152  L-Asparagine
C00158  Citrate
C00183  L-Valine
C00186  (S)-Lactate
C00197  3-Phospho-D-glycerate
C00311  Isocitrate
C00354  D-Fructose 1,6-bisphosphate
C00407  L-Isoleucine
C00631  2-Phospho-D-glycerate
C00665  beta-D-Fructose 2,6-bisphosphate
C00704  Superoxide
Reference
PMID:23279446
  Authors
Soga T
  Title
Cancer metabolism: key players in metabolic reprogramming.
  Journal
Cancer Sci 104:275-81 (2013)
DOI:10.1111/cas.12085
Reference
PMID:19460998
  Authors
Vander Heiden MG, Cantley LC, Thompson CB
  Title
Understanding the Warburg effect: the metabolic requirements of cell proliferation.
  Journal
Science 324:1029-33 (2009)
DOI:10.1126/science.1160809
Reference
PMID:23071355
  Authors
Teicher BA, Linehan WM, Helman LJ
  Title
Targeting cancer metabolism.
  Journal
Clin Cancer Res 18:5537-45 (2012)
DOI:10.1158/1078-0432.CCR-12-2587
Reference
PMID:21127244
  Authors
Levine AJ, Puzio-Kuter AM
  Title
The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes.
  Journal
Science 330:1340-4 (2010)
DOI:10.1126/science.1193494
Reference
PMID:24079832
  Authors
Amoedo ND, Valencia JP, Rodrigues MF, Galina A, Rumjanek FD
  Title
How does the metabolism of tumour cells differ from that of normal cells.
  Journal
Biosci Rep 33:e00080 (2013)
DOI:10.1042/BSR20130066
Reference
PMID:21258394
  Authors
Cairns RA, Harris IS, Mak TW
  Title
Regulation of cancer cell metabolism.
  Journal
Nat Rev Cancer 11:85-95 (2011)
DOI:10.1038/nrc2981
Reference
PMID:22237205
  Authors
Munoz-Pinedo C, El Mjiyad N, Ricci JE
  Title
Cancer metabolism: current perspectives and future directions.
  Journal
Cell Death Dis 3:e248 (2012)
DOI:10.1038/cddis.2011.123
Reference
PMID:22156302
  Authors
Cairns RA, Harris I, McCracken S, Mak TW
  Title
Cancer cell metabolism.
  Journal
Cold Spring Harb Symp Quant Biol 76:299-311 (2011)
DOI:10.1101/sqb.2011.76.012856
Reference
PMID:18538731
  Authors
Kroemer G, Pouyssegur J
  Title
Tumor cell metabolism: cancer's Achilles' heel.
  Journal
Cancer Cell 13:472-82 (2008)
DOI:10.1016/j.ccr.2008.05.005
Reference
PMID:18177721
  Authors
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB
  Title
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
  Journal
Cell Metab 7:11-20 (2008)
DOI:10.1016/j.cmet.2007.10.002
Reference
PMID:21508971
  Authors
Koppenol WH, Bounds PL, Dang CV
  Title
Otto Warburg's contributions to current concepts of cancer metabolism.
  Journal
Nat Rev Cancer 11:325-37 (2011)
DOI:10.1038/nrc3038
Reference
PMID:21801601
  Authors
Fogg VC, Lanning NJ, Mackeigan JP
  Title
Mitochondria in cancer: at the crossroads of life and death.
  Journal
Chin J Cancer 30:526-39 (2011)
DOI:10.5732/cjc.011.10018
Reference
PMID:16982728
  Authors
Kim JW, Dang CV
  Title
Cancer's molecular sweet tooth and the Warburg effect.
  Journal
Cancer Res 66:8927-30 (2006)
DOI:10.1158/0008-5472.CAN-06-1501
Reference
PMID:18766298
  Authors
Yeung SJ, Pan J, Lee MH
  Title
Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer.
  Journal
Cell Mol Life Sci 65:3981-99 (2008)
DOI:10.1007/s00018-008-8224-x
Reference
PMID:23897900
  Authors
Li B, Simon MC
  Title
Molecular Pathways: Targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer.
  Journal
Clin Cancer Res 19:5835-41 (2013)
DOI:10.1158/1078-0432.CCR-12-3629
Reference
PMID:22307140
  Authors
Shen L, Sun X, Fu Z, Yang G, Li J, Yao L
  Title
The fundamental role of the p53 pathway in tumor metabolism and its implication in tumor therapy.
  Journal
Clin Cancer Res 18:1561-7 (2012)
DOI:10.1158/1078-0432.CCR-11-3040
Reference
PMID:19270154
  Authors
Jones RG, Thompson CB
  Title
Tumor suppressors and cell metabolism: a recipe for cancer growth.
  Journal
Genes Dev 23:537-48 (2009)
DOI:10.1101/gad.1756509
Reference
PMID:21340684
  Authors
Maddocks OD, Vousden KH
  Title
Metabolic regulation by p53.
  Journal
J Mol Med (Berl) 89:237-45 (2011)
DOI:10.1007/s00109-011-0735-5
Reference
PMID:22750268
  Authors
Chen JQ, Russo J
  Title
Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells.
  Journal
Biochim Biophys Acta 1826:370-84 (2012)
DOI:10.1016/j.bbcan.2012.06.004
Reference
PMID:20520704
  Authors
Kaelin WG Jr, Thompson CB
  Title
Q&A: Cancer: clues from cell metabolism.
  Journal
Nature 465:562-4 (2010)
DOI:10.1038/465562a
Reference
PMID:24113830
  Authors
Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G
  Title
Metabolic targets for cancer therapy.
  Journal
Nat Rev Drug Discov 12:829-46 (2013)
DOI:10.1038/nrd4145
Reference
PMID:24738035
  Authors
Phan LM, Yeung SC, Lee MH
  Title
Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies.
  Journal
Cancer Biol Med 11:1-19 (2014)
DOI:10.7497/j.issn.2095-3941.2014.01.001
Reference
PMID:22101401
  Authors
Icard P, Poulain L, Lincet H
  Title
Understanding the central role of citrate in the metabolism of cancer cells.
  Journal
Biochim Biophys Acta 1825:111-6 (2012)
DOI:10.1016/j.bbcan.2011.10.007
Reference
PMID:22349059
  Authors
Daye D, Wellen KE
  Title
Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis.
  Journal
Semin Cell Dev Biol 23:362-9 (2012)
DOI:10.1016/j.semcdb.2012.02.002
Reference
PMID:23018234
  Authors
Chiarugi A, Dolle C, Felici R, Ziegler M
  Title
The NAD metabolome--a key determinant of cancer cell biology.
  Journal
Nat Rev Cancer 12:741-52 (2012)
DOI:10.1038/nrc3340
Reference
PMID:24398961
  Authors
Guarente L
  Title
The many faces of sirtuins: Sirtuins and the Warburg effect.
  Journal
Nat Med 20:24-5 (2014)
DOI:10.1038/nm.3438
Reference
PMID:15916903
  Authors
Fuchs BC, Bode BP
  Title
Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?
  Journal
Semin Cancer Biol 15:254-66 (2005)
DOI:10.1016/j.semcancer.2005.04.005
Related
pathway
mmu00010  Glycolysis / Gluconeogenesis
mmu00020  Citrate cycle (TCA cycle)
mmu00030  Pentose phosphate pathway
mmu00190  Oxidative phosphorylation
mmu00250  Alanine, aspartate and glutamate metabolism
mmu00260  Glycine, serine and threonine metabolism
mmu00330  Arginine and proline metabolism
mmu01212  Fatty acid metabolism
mmu04010  MAPK signaling pathway
mmu04066  HIF-1 signaling pathway
mmu04150  mTOR signaling pathway
mmu04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
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