Entry Name Central carbon metabolism in cancer - Loxodonta africana (African savanna elephant)
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 lav05230 Central carbon metabolism in cancer
Ortholog table Organism Loxodonta africana (African savanna elephant) [GN:
lav ]
Gene 100677089 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
100669209 SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593 ]
100653931 PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161 ] [EC:1.2.4.1 ]
100660992 PDHA1; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
100655808 PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X1 [KO:K12077 ] [EC:2.7.11.2 ]
100665580 SLC1A5; LOW QUALITY PROTEIN: neutral amino acid transporter B(0) [KO:K05616 ]
100657948 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100658340 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100666266 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
100653731 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
100665045 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100675496 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
100677101 SLC7A5; large neutral amino acids transporter small subunit 1 [KO:K13780 ]
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 lav00250 Alanine, aspartate and glutamate metabolism
lav00260 Glycine, serine and threonine metabolism
lav00330 Arginine and proline metabolism
KO pathway LinkDB All DBs
