Entry Name Choline metabolism in cancer - Sorex araneus (European shrew)
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 Sorex araneus (European shrew) [GN:
sara ]
Gene 101544020 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
101550972 SOS1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099 ]
101554760 RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732 ]
101542917 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101556597 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101548304 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
101547106 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101541868 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101540938 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
101546455 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
101559390 WASF1; wiskott-Aldrich syndrome protein family member 1 [KO:K05753 ]
101538780 WASF2; wiskott-Aldrich syndrome protein family member 2 isoform X1 [KO:K05748 ]
101540458 WASF3; wiskott-Aldrich syndrome protein family member 3 isoform X1 [KO:K06083 ]
101543854 SLC44A1; choline transporter-like protein 1 isoform X1 [KO:K06515 ]
101541220 SLC44A4; choline transporter-like protein 4 isoform X1 [KO:K15377 ]
101542167 SLC44A2; choline transporter-like protein 2 isoform X2 [KO:K15377 ]
101545860 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [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
