KEGG   PATHWAY: rro05230
Entry
rro05230                    Pathway                                
Name
Central carbon metabolism in cancer - Rhinopithecus roxellana (golden snub-nosed monkey)
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
rro05230  Central carbon metabolism in cancer
rro05230

Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104669015  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
104660535  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
104671144  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
104663550  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
104679850  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
104682411  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
104660196  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
104673517  PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077] [EC:2.7.11.2]
104661662  TP53; cellular tumor antigen p53 [KO:K04451]
104655473  protein SCO2 homolog, mitochondrial isoform X2 [KO:K23755]
104673399  SLC1A5; neutral amino acid transporter B(0) isoform X1 [KO:K05616]
104672643  SIRT3; NAD-dependent protein deacetylase sirtuin-3, mitochondrial isoform X1 [KO:K11413] [EC:2.3.1.286]
104654987  SLC16A3; monocarboxylate transporter 4 [KO:K08180]
104665427  SIRT6; NAD-dependent protein deacetylase sirtuin-6 isoform X1 [KO:K11416] [EC:2.3.1.286]
104674798  MYC; myc proto-oncogene protein [KO:K04377]
104655242  HIF1A; hypoxia-inducible factor 1-alpha isoform X2 [KO:K08268]
104658855  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
104682633  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
104653928  RET; proto-oncogene tyrosine-protein kinase receptor Ret isoform X1 [KO:K05126] [EC:2.7.10.1]
104675886  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
104674848  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
104676442  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
104661599  NTRK3; NT-3 growth factor receptor isoform X3 [KO:K05101] [EC:2.7.10.1]
104658857  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
104670408  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
104679640  FGFR1; fibroblast growth factor receptor 1 isoform X2 [KO:K04362] [EC:2.7.10.1]
104675847  FGFR2; fibroblast growth factor receptor 2 isoform X3 [KO:K05093] [EC:2.7.10.1]
104678934  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
104661678  FLT3; receptor-type tyrosine-protein kinase FLT3 isoform X1 [KO:K05092] [EC:2.7.10.1]
104654600  HRAS; GTPase HRas isoform X1 [KO:K02833]
104670041  KRAS; GTPase KRas isoform X1 [KO:K07827]
104669078  NRAS; GTPase NRas [KO:K07828]
104673299  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
104662575  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104665487  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104676897  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104681150  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104673669  GLS2; glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
104675281  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
104667047  G6PD; glucose-6-phosphate 1-dehydrogenase isoform X5 [KO:K00036] [EC:1.1.1.49 1.1.1.363]
104661961  HKDC1; hexokinase HKDC1 isoform X1 [KO:K00844] [EC:2.7.1.1]
104661963  HK1; hexokinase-1 isoform X2 [KO:K00844] [EC:2.7.1.1]
104680441  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
104674833  HK2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
104659937  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
104678915  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
104654845  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
104671137  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
104675028  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
104658090  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
104682816  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
104660891  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
104670887  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
104667649  L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
104667650  LDHAL6A; L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
104667673  LOW QUALITY PROTEIN: L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
104670932  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
104678767  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
104654583  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
104657046  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
104667485  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
104669589  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
104657497  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
104667647  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
104682736  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
115894908  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
104672972  IDH1; isocitrate dehydrogenase [NADP] cytoplasmic [KO:K00031] [EC:1.1.1.42]
104674338  IDH2; isocitrate dehydrogenase [NADP], mitochondrial isoform X2 [KO:K00031] [EC:1.1.1.42]
104658981  TIGAR; fructose-2,6-bisphosphatase TIGAR [KO:K14634] [EC:3.1.3.46]
104675158  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
104663050  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104665061  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104670605  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104662124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104675620  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104680672  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104673041  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104676121  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654186  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
115893905  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654362  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
104655997  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
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
rro00010  Glycolysis / Gluconeogenesis
rro00020  Citrate cycle (TCA cycle)
rro00030  Pentose phosphate pathway
rro00190  Oxidative phosphorylation
rro00250  Alanine, aspartate and glutamate metabolism
rro00260  Glycine, serine and threonine metabolism
rro00330  Arginine and proline metabolism
rro01212  Fatty acid metabolism
rro04010  MAPK signaling pathway
rro04066  HIF-1 signaling pathway
rro04150  mTOR signaling pathway
rro04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
LinkDB

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