KEGG   PATHWAY: bacu05230
Entry
bacu05230                   Pathway                                
Name
Central carbon metabolism in cancer - Balaenoptera acutorostrata scammoni (minke whale)
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
bacu05230  Central carbon metabolism in cancer
bacu05230

Organism
Balaenoptera acutorostrata scammoni (minke whale) [GN:bacu]
Gene
103013089  solute carrier family 2, facilitated glucose transporter member 1-like [KO:K07299]
103000646  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
103004735  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
102999998  PKM; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
103016773  PDHA1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
103021119  PDHB; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
103016999  PDK1; pyruvate dehydrogenase kinase 1 [KO:K12077] [EC:2.7.11.2]
103003426  TP53; tumor protein p53 [KO:K04451]
103013012  protein SCO2 homolog, mitochondrial-like [KO:K23755]
102998561  SLC1A5; solute carrier family 1 member 5 [KO:K05616]
103011694  SIRT3; sirtuin 3 [KO:K11413] [EC:2.3.1.286]
103018145  SLC16A3; solute carrier family 16 member 3 [KO:K08180]
103017769  SIRT6; sirtuin 6 [KO:K11416] [EC:2.3.1.286]
103016933  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103008124  HIF1A; hypoxia inducible factor 1 alpha subunit [KO:K08268]
102999027  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
103002086  MET; MET proto-oncogene, receptor tyrosine kinase [KO:K05099] [EC:2.7.10.1]
103006627  RET; ret proto-oncogene [KO:K05126] [EC:2.7.10.1]
103017029  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103002640  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
103003654  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
103011612  NTRK3; neurotrophic receptor tyrosine kinase 3 [KO:K05101] [EC:2.7.10.1]
102998016  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
103019883  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
103017733  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
103012184  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
103002473  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
103008462  FLT3; fms related tyrosine kinase 3 [KO:K05092] [EC:2.7.10.1]
103006545  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103015457  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103004931  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103014337  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103017381  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103018627  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102999619  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103002590  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103020183  GLS; glutaminase [KO:K01425] [EC:3.5.1.2]
103003592  GLS2; glutaminase 2 [KO:K01425] [EC:3.5.1.2]
103016715  G6PD; glucose-6-phosphate dehydrogenase [KO:K00036] [EC:1.1.1.49 1.1.1.363]
103000123  HK1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
103000583  HKDC1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
103011120  HK3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
103005558  HK2; hexokinase 2 [KO:K00844] [EC:2.7.1.1]
103005952  PFKP; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
103009421  PFKM; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
103014534  PFKL; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
103007307  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
103020160  phosphoglycerate mutase 2-like [KO:K01834] [EC:5.4.2.11]
103015334  L-lactate dehydrogenase A-like 6B-like [KO:K00016] [EC:1.1.1.27]
103006573  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
103008045  LDHB; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
103018917  LDHC; lactate dehydrogenase C [KO:K00016] [EC:1.1.1.27]
103019556  LDHA; lactate dehydrogenase A [KO:K00016] [EC:1.1.1.27]
102998067  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
103006265  LDHAL6A; lactate dehydrogenase A like 6A [KO:K00016] [EC:1.1.1.27]
103019163  IDH1; isocitrate dehydrogenase (NADP(+)) 1, cytosolic [KO:K00031] [EC:1.1.1.42]
103003463  IDH2; isocitrate dehydrogenase (NADP(+)) 2, mitochondrial [KO:K00031] [EC:1.1.1.42]
103002696  TIGAR; TP53 induced glycolysis regulatory phosphatase [KO:K14634] [EC:3.1.3.46]
102998704  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103012691  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103012931  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103014043  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103008077  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103009307  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103007464  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103002026  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103013147  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103004139  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103004460  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103009963  SLC7A5; solute carrier family 7 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
  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
bacu00010  Glycolysis / Gluconeogenesis
bacu00020  Citrate cycle (TCA cycle)
bacu00030  Pentose phosphate pathway
bacu00190  Oxidative phosphorylation
bacu00250  Alanine, aspartate and glutamate metabolism
bacu00260  Glycine, serine and threonine metabolism
bacu00330  Arginine and proline metabolism
bacu01212  Fatty acid metabolism
bacu04010  MAPK signaling pathway
bacu04066  HIF-1 signaling pathway
bacu04150  mTOR signaling pathway
bacu04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
LinkDB

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