Entry |
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Name |
Choline metabolism in cancer - Pongo abelii (Sumatran orangutan)
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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.
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Class |
Human Diseases; Cancer: overview
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Pathway map |

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Organism |
Pongo abelii (Sumatran orangutan) [GN: pon]
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Gene |
100440212 | PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359] |
100451493 | RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732] |
100432846 | PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153] |
100453779 | PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153] |
103889133 | PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153] |
100174298 | PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649] |
100173589 | PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649] |
100437617 | PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649] |
100455169 | EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205] |
100452449 | WAS; LOW QUALITY PROTEIN: wiskott-Aldrich syndrome protein [KO:K05747] |
112129584 | RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861] |
100174148 | WASF1; wiskott-Aldrich syndrome protein family member 1 [KO:K05753] |
100437132 | LOW QUALITY PROTEIN: wiskott-Aldrich syndrome protein family member 2-like [KO:K05748] |
100447501 | WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748] |
100445243 | WASF3; wiskott-Aldrich syndrome protein family member 3 isoform X1 [KO:K06083] |
100457648 | SLC5A7; high affinity choline transporter 1 isoform X1 [KO:K14387] |
100449286 | SLC44A1; choline transporter-like protein 1 isoform X1 [KO:K06515] |
100443199 | SLC44A5; choline transporter-like protein 5 isoform X1 [KO:K15377] |
100455825 | SLC44A3; choline transporter-like protein 3 isoform X1 [KO:K15282] |
100436901 | SLC22A1; solute carrier family 22 member 1 isoform X1 [KO:K08198] |
100449383 | SLC22A5; solute carrier family 22 member 5 isoform X1 [KO:K08202] |
100456472 | SLC22A4; solute carrier family 22 member 4 isoform X1 [KO:K08202] |
100450941 | PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11] |
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Compound |
C00093 | sn-Glycerol 3-phosphate |
C00670 | sn-Glycero-3-phosphocholine |
C04230 | 1-Acyl-sn-glycero-3-phosphocholine |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Glunde K, Bhujwalla ZM, Ronen SM |
Title |
Choline metabolism in malignant transformation. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Foster DA |
Title |
Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Ridgway ND |
Title |
The role of phosphatidylcholine and choline metabolites to cell proliferation and survival. |
Journal |
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Reference |
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Authors |
Awwad HM, Geisel J, Obeid R |
Title |
The role of choline in prostate cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Ackerstaff E, Glunde K, Bhujwalla ZM |
Title |
Choline phospholipid metabolism: a target in cancer cells? |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Foster DA, Xu L |
Title |
Phospholipase D in cell proliferation and cancer. |
Journal |
Mol Cancer Res 1:789-800 (2003) |
Reference |
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Authors |
Zhou H, Huang S |
Title |
mTOR signaling in cancer cell motility and tumor metastasis. |
Journal |
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Related pathway |
pon04810 | Regulation of actin cytoskeleton |
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KO pathway |
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LinkDB |
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