KEGG   PATHWAY: mcal05230
Entry
mcal05230                   Pathway                                
Name
Central carbon metabolism in cancer - Mus caroli (Ryukyu 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
mcal05230  Central carbon metabolism in cancer
mcal05230

Organism
Mus caroli (Ryukyu mouse) [GN:mcal]
Gene
110292203  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
110291094  Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
110305090  Gck; glucokinase isoform X1 [KO:K12407] [EC:2.7.1.2]
110301002  Pkm; pyruvate kinase PKM isoform X2 [KO:K00873] [EC:2.7.1.40]
110291389  Pdha2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
110286532  Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
110309029  Pdhb; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
110312693  Pdk1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077] [EC:2.7.11.2]
110305297  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110310005  protein SCO2 homolog, mitochondrial [KO:K23755]
110297287  Slc1a5; neutral amino acid transporter B(0) [KO:K05616]
110297529  Sirt3; NAD-dependent protein deacetylase sirtuin-3, mitochondrial isoform X1 [KO:K11413] [EC:2.3.1.286]
110306105  Slc16a3; monocarboxylate transporter 4 isoform X1 [KO:K08180]
110303259  Sirt6; NAD-dependent protein deacetylase sirtuin-6 isoform X2 [KO:K11416] [EC:2.3.1.286]
110310583  Myc; myc proto-oncogene protein [KO:K04377]
110306746  Hif1a; hypoxia-inducible factor 1-alpha isoform X5 [KO:K08268]
110294693  Kit; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
110295947  Met; hepatocyte growth factor receptor isoform X2 [KO:K05099] [EC:2.7.10.1]
110295751  Ret; proto-oncogene tyrosine-protein kinase receptor Ret [KO:K05126] [EC:2.7.10.1]
110304228  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
110304771  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
110290875  Ntrk1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
110297619  Ntrk3; NT-3 growth factor receptor isoform X5 [KO:K05101] [EC:2.7.10.1]
110295292  Pdgfra; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
110284880  Pdgfrb; platelet-derived growth factor receptor beta isoform X2 [KO:K05089] [EC:2.7.10.1]
110299550  Fgfr1; fibroblast growth factor receptor 1 isoform X2 [KO:K04362] [EC:2.7.10.1]
110299396  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
110293909  Fgfr3; fibroblast growth factor receptor 3 isoform X8 [KO:K05094] [EC:2.7.10.1]
110294537  Flt3; receptor-type tyrosine-protein kinase FLT3 [KO:K05092] [EC:2.7.10.1]
110297313  Hras; GTPase HRas isoform X2 [KO:K02833]
110296194  Kras; GTPase KRas isoform X1 [KO:K07827]
110290873  Nras; GTPase NRas [KO:K07828]
110296919  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110301502  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110303196  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110297836  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110311382  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110292585  Gls; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
110304085  Gls2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
110294683  glucose-6-phosphate 1-dehydrogenase 2 [KO:K00036] [EC:1.1.1.49 1.1.1.363]
110287186  G6pd; glucose-6-phosphate 1-dehydrogenase [KO:K00036] [EC:1.1.1.49 1.1.1.363]
110296267  Hk2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
110302692  Hk1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
110303354  Hkdc1; putative hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
110307543  Hk3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
110307877  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
110302996  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
110310722  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type isoform X2 [KO:K00850] [EC:2.7.1.11]
110285594  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
110305623  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
110284102  Ldhal6b; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
110296103  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
110297508  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
110297509  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
110296028  Ldhb; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
110297563  Idh2; isocitrate dehydrogenase [NADP], mitochondrial [KO:K00031] [EC:1.1.1.42]
110295345  Idh1; isocitrate dehydrogenase [NADP] cytoplasmic [KO:K00031] [EC:1.1.1.42]
110284994  isocitrate dehydrogenase [NADP] cytoplasmic [KO:K00031] [EC:1.1.1.42]
110296700  Tigar; fructose-2,6-bisphosphatase TIGAR [KO:K14634] [EC:3.1.3.46]
110285202  Pten; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
110290798  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110292183  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110301355  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110308009  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110299855  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
110292624  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110297609  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110294471  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110307022  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110292680  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110299835  Slc7a5; large neutral amino acids transporter small subunit 1 [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
  Authors
Soga T
  Title
Cancer metabolism: key players in metabolic reprogramming.
  Journal
Cancer Sci 104:275-81 (2013)
DOI:10.1111/cas.12085
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
mcal00010  Glycolysis / Gluconeogenesis
mcal00020  Citrate cycle (TCA cycle)
mcal00030  Pentose phosphate pathway
mcal00190  Oxidative phosphorylation
mcal00250  Alanine, aspartate and glutamate metabolism
mcal00260  Glycine, serine and threonine metabolism
mcal00330  Arginine and proline metabolism
mcal01212  Fatty acid metabolism
mcal04010  MAPK signaling pathway
mcal04066  HIF-1 signaling pathway
mcal04150  mTOR signaling pathway
mcal04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
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