Entry Name Choline metabolism in cancer - Phyllostomus hastatus (greater spear-nosed bat)
Description Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS and PI3K-AKT pathways, and transcription factors associated with oncogenesis such as hypoxia-inducible factor 1 (HIF1) mediate overexpression and activation of choline cycle enzymes, which causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These products of choline phospholipid metabolism, such as phosphocholine (PCho), diacylglycerol (DAG) and phosphatidic acid, may function as second messengers that are essential for the mitogenic activity of growth factors, particularly in the activation of the ras-raf-1-MAPK cascade and protein kinase C pathway.
Class Human Diseases; Cancer: overviewBRITE hierarchy
Pathway map Ortholog table Organism Phyllostomus hastatus (greater spear-nosed bat) [GN:
phas ]
Gene 123810721 PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359 ]
123823464 RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732 ]
123826750 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
123830565 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
123831922 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
123828291 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
123824527 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
123832298 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
123807542 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
123817374 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
123821679 WASF1; wiskott-Aldrich syndrome protein family member 1 isoform X1 [KO:K05753 ]
123831774 WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748 ]
123822752 WASF3; wiskott-Aldrich syndrome protein family member 3 isoform X1 [KO:K06083 ]
123819671 SLC44A1; choline transporter-like protein 1 isoform X1 [KO:K06515 ]
123828231 SLC44A2; choline transporter-like protein 2 isoform X1 [KO:K15377 ]
123822167 SLC22A3; solute carrier family 22 member 3 isoform X1 [KO:K08200 ]
123812359 SLC22A4; solute carrier family 22 member 4 isoform X1 [KO:K08202 ]
123809018 SLC22A5; solute carrier family 22 member 5 isoform X1 [KO:K08202 ]
123814793 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
Compound C00093 sn-Glycerol 3-phosphate
C00670 sn-Glycero-3-phosphocholine
C04230 1-Acyl-sn-glycero-3-phosphocholine
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Glunde K, Bhujwalla ZM, Ronen SM
Title Choline metabolism in malignant transformation.
Journal Reference Authors Beloueche-Babari M, Chung YL, Al-Saffar NM, Falck-Miniotis M, Leach MO
Title Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy.
Journal Reference Authors Abalsamo L, Spadaro F, Bozzuto G, Paris L, Cecchetti S, Lugini L, Iorio E, Molinari A, Ramoni C, Podo F
Title Inhibition of phosphatidylcholine-specific phospholipase C results in loss of mesenchymal traits in metastatic breast cancer cells.
Journal Reference Authors Foster DA
Title Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells.
Journal Reference Authors Beloueche-Babari M, Jackson LE, Al-Saffar NM, Eccles SA, Raynaud FI, Workman P, Leach MO, Ronen SM
Title Identification of magnetic resonance detectable metabolic changes associated with inhibition of phosphoinositide 3-kinase signaling in human breast cancer cells.
Journal Reference Authors Ridgway ND
Title The role of phosphatidylcholine and choline metabolites to cell proliferation and survival.
Journal Reference Authors Awwad HM, Geisel J, Obeid R
Title The role of choline in prostate cancer.
Journal Reference Authors Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D'Ascenzo S, Millimaggi D, Pavan A, Dolo V, Canevari S, Podo F
Title Alterations of choline phospholipid metabolism in ovarian tumor progression.
Journal Reference Authors Ackerstaff E, Glunde K, Bhujwalla ZM
Title Choline phospholipid metabolism: a target in cancer cells?
Journal Reference Authors Park JB, Lee CS, Jang JH, Ghim J, Kim YJ, You S, Hwang D, Suh PG, Ryu SH
Title Phospholipase signalling networks in cancer.
Journal Reference Authors Yalcin A, Clem B, Makoni S, Clem A, Nelson K, Thornburg J, Siow D, Lane AN, Brock SE, Goswami U, Eaton JW, Telang S, Chesney J
Title Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling.
Journal Reference Authors Glunde K, Jiang L, Moestue SA, Gribbestad IS
Title MRS and MRSI guidance in molecular medicine: targeting and monitoring of choline and glucose metabolism in cancer.
Journal Reference Authors Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, Armstrong MD, Arteaga CL, Lindsley CW, Brown HA
Title Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.
Journal Reference Authors Foster DA, Xu L
Title Phospholipase D in cell proliferation and cancer.
Journal Mol Cancer Res 1:789-800 (2003)
Reference Authors Zhou H, Huang S
Title mTOR signaling in cancer cell motility and tumor metastasis.
Journal Related KO pathway LinkDB All DBs
