Entry Name Central carbon metabolism in cancer
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: overviewBRITE hierarchy
Pathway map ko05230 Central carbon metabolism in cancer
Orthology K00161 PDHA; pyruvate dehydrogenase E1 component subunit alpha [EC:1.2.4.1 ]
K00162 PDHB; pyruvate dehydrogenase E1 component subunit beta [EC:1.2.4.1 ]
K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01834 PGAM, gpmA; 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase [EC:5.4.2.11 ]
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03176 NTRK1, TRKA; neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1 ]
K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1 ]
K04363 PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04377 MYC; Myc proto-oncogene protein
K04451 TP53, P53; tumor protein p53
K05083 ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1 ]
K05089 PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1 ]
K05091 KIT, SCFR, CD117; proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1 ]
K05093 FGFR2, CD332; fibroblast growth factor receptor 2 [EC:2.7.10.1 ]
K05094 FGFR3, CD333; fibroblast growth factor receptor 3 [EC:2.7.10.1 ]
K05099 MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1 ]
K05101 NTRK3, TRKC; neurotrophic tyrosine kinase, receptor type 3 [EC:2.7.10.1 ]
K05616 SLC1A5; solute carrier family 1 (neutral amino acid transporter), member 5
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07299 SLC2A1, GLUT1; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K07593 SLC2A2, GLUT2; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 2
K07827 KRAS, KRAS2; GTPase KRas
K08180 SLC16A3; MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 3
K08268 HIF1A; hypoxia-inducible factor 1 alpha
K11413 SIRT3, SIR2L3; NAD-dependent protein deacetylase sirtuin 3 [EC:2.3.1.286 ]
K11416 SIRT6, SIR2L6; NAD-dependent protein deacetylase sirtuin 6 [EC:2.3.1.286 ]
K13780 SLC7A5, LAT1; solute carrier family 7 (L-type amino acid transporter), member 5
Compound C00354 D-Fructose 1,6-bisphosphate
C00665 beta-D-Fructose 2,6-bisphosphate
Reference Authors Soga T
Title Cancer metabolism: key players in metabolic reprogramming.
Journal Reference Authors Vander Heiden MG, Cantley LC, Thompson CB
Title Understanding the Warburg effect: the metabolic requirements of cell proliferation.
Journal Reference Authors Teicher BA, Linehan WM, Helman LJ
Title Targeting cancer metabolism.
Journal Reference Authors Levine AJ, Puzio-Kuter AM
Title The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes.
Journal 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 Reference Authors Cairns RA, Harris IS, Mak TW
Title Regulation of cancer cell metabolism.
Journal Reference Authors Munoz-Pinedo C, El Mjiyad N, Ricci JE
Title Cancer metabolism: current perspectives and future directions.
Journal Reference Authors Cairns RA, Harris I, McCracken S, Mak TW
Title Cancer cell metabolism.
Journal Reference Authors Kroemer G, Pouyssegur J
Title Tumor cell metabolism: cancer's Achilles' heel.
Journal Reference Authors DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB
Title The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
Journal Reference Authors Koppenol WH, Bounds PL, Dang CV
Title Otto Warburg's contributions to current concepts of cancer metabolism.
Journal Reference Authors Fogg VC, Lanning NJ, Mackeigan JP
Title Mitochondria in cancer: at the crossroads of life and death.
Journal Reference Authors Kim JW, Dang CV
Title Cancer's molecular sweet tooth and the Warburg effect.
Journal 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 Reference Authors Li B, Simon MC
Title Molecular Pathways: Targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer.
Journal 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 Reference Authors Jones RG, Thompson CB
Title Tumor suppressors and cell metabolism: a recipe for cancer growth.
Journal Reference Authors Maddocks OD, Vousden KH
Title Metabolic regulation by p53.
Journal 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 Reference Authors Kaelin WG Jr, Thompson CB
Title Q&A: Cancer: clues from cell metabolism.
Journal Reference Authors Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G
Title Metabolic targets for cancer therapy.
Journal Reference Authors Phan LM, Yeung SC, Lee MH
Title Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies.
Journal Reference Authors Icard P, Poulain L, Lincet H
Title Understanding the central role of citrate in the metabolism of cancer cells.
Journal Reference Authors Daye D, Wellen KE
Title Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis.
Journal Reference Authors Chiarugi A, Dolle C, Felici R, Ziegler M
Title The NAD metabolome--a key determinant of cancer cell biology.
Journal Reference Authors Guarente L
Title The many faces of sirtuins: Sirtuins and the Warburg effect.
Journal Reference Authors Fuchs BC, Bode BP
Title Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?
Journal Related ko00010 Glycolysis / Gluconeogenesis
ko00250 Alanine, aspartate and glutamate metabolism
ko00260 Glycine, serine and threonine metabolism
ko00330 Arginine and proline metabolism
