KEGG   PATHWAY: mdo05230
Entry
mdo05230                    Pathway                                
Name
Central carbon metabolism in cancer - Monodelphis domestica (gray short-tailed opossum)
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
mdo05230  Central carbon metabolism in cancer
mdo05230

Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100026702  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
100010342  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
100030125  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
100017841  PKM; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
100014220  PDHA1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
100014556  PDHB; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
100617164  PDK1; pyruvate dehydrogenase kinase 1 [KO:K12077] [EC:2.7.11.2]
100029831  pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial-like [KO:K12077] [EC:2.7.11.2]
497248  TP53; tumor protein p53 [KO:K04451]
100021149  SLC1A5; solute carrier family 1 member 5 [KO:K05616]
100030763  SIRT3; sirtuin 3 [KO:K11413] [EC:2.3.1.286]
100029717  SLC16A3; solute carrier family 16 member 3 [KO:K08180]
100022578  SIRT6; sirtuin 6 [KO:K11416] [EC:2.3.1.286]
100032344  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100027212  HIF1A; hypoxia inducible factor 1 alpha subunit [KO:K08268]
100017501  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
100013788  MET; MET proto-oncogene, receptor tyrosine kinase [KO:K05099] [EC:2.7.10.1]
100016023  RET; ret proto-oncogene [KO:K05126] [EC:2.7.10.1]
100029625  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100017172  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
100618744  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
100013667  NTRK3; neurotrophic receptor tyrosine kinase 3 [KO:K05101] [EC:2.7.10.1]
100013088  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
100028943  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
100029852  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
100025727  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
100023287  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
100025262  FLT3; fms related tyrosine kinase 3 [KO:K05092] [EC:2.7.10.1]
100032921  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
554186  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
554197  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100022523  GTPase NRas-like [KO:K07828]
100015410  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100018410  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100018044  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100024307  GLS2; glutaminase 2 [KO:K01425] [EC:3.5.1.2]
100021586  GLS; glutaminase [KO:K01425] [EC:3.5.1.2]
100012365  G6PD; glucose-6-phosphate dehydrogenase [KO:K00036] [EC:1.1.1.49 1.1.1.363]
100032849  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
100031793  HK3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
100031311  HK1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
100015984  HKDC1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
100022041  PFKP; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
100023492  PFKL; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
100016520  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
100025819  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
100022730  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
103096982  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
100028290  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
554182  LDHB; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
100012604  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
503513  LDHA; lactate dehydrogenase A [KO:K00016] [EC:1.1.1.27]
100028279  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
100031420  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
751083  IDH1; isocitrate dehydrogenase (NADP(+)) 1, cytosolic [KO:K00031] [EC:1.1.1.42]
100015156  IDH2; isocitrate dehydrogenase (NADP(+)) 2, mitochondrial [KO:K00031] [EC:1.1.1.42]
100019695  TIGAR; TP53 induced glycolysis regulatory phosphatase [KO:K14634] [EC:3.1.3.46]
100013036  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100010412  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100017332  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100024769  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
100019317  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100032726  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
100616957  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
100014564  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100019947  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100027373  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100619675  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
100025636  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
mdo00010  Glycolysis / Gluconeogenesis
mdo00020  Citrate cycle (TCA cycle)
mdo00030  Pentose phosphate pathway
mdo00190  Oxidative phosphorylation
mdo00250  Alanine, aspartate and glutamate metabolism
mdo00260  Glycine, serine and threonine metabolism
mdo00330  Arginine and proline metabolism
mdo01212  Fatty acid metabolism
mdo04010  MAPK signaling pathway
mdo04066  HIF-1 signaling pathway
mdo04150  mTOR signaling pathway
mdo04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
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