KEGG   PATHWAY: ko05231Help
ko05231                     Pathway                                

Choline metabolism in cancer
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.
Human Diseases; Cancers: Overview
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Pathway map
ko05231  Choline metabolism in cancer

Ortholog table
K04357  epidermal growth factor
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K05450  platelet derived growth factor C/D
K04361  epidermal growth factor receptor [EC:]
K04363  platelet-derived growth factor receptor alpha [EC:]
K05089  platelet-derived growth factor receptor beta [EC:]
K04364  growth factor receptor-binding protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K08732  ral guanine nucleotide dissociation stimulator
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:]
K16342  cytosolic phospholipase A2 [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K06276  3-phosphoinositide dependent protein kinase-1 [EC:]
K04456  RAC serine/threonine-protein kinase [EC:]
K07206  tuberous sclerosis 1
K07207  tuberous sclerosis 2
K07208  Ras homolog enriched in brain
K07203  serine/threonine-protein kinase mTOR [EC:]
K04688  ribosomal protein S6 kinase beta [EC:]
K07205  eukaryotic translation initiation factor 4E binding protein 1
K00889  1-phosphatidylinositol-4-phosphate 5-kinase [EC:]
K05747  Wiskott-Aldrich syndrome protein
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K05753  WAS protein family, member 1
K05748  WAS protein family, member 2
K06083  WAS protein family, member 3
K04684  transcription factor Sp1
K01115  phospholipase D1/2 [EC:]
K14387  solute carrier family 5 (high affinity choline transporter), member 7
K06515  solute carrier family 44 (choline transporter-like protein), member 1
K15377  solute carrier family 44 (choline transporter-like protein), member 2/4/5
K15282  solute carrier family 44 (choline transporter-like protein), member 3
K08198  MFS transporter, OCT family, solute carrier family 22 (organic cation transporter), member 1
K08199  MFS transporter, OCT family, solute carrier family 22 (organic cation transporter), member 2
K08200  MFS transporter, OCT family, solute carrier family 22 (organic cation transporter), member 3
K08202  MFS transporter, OCT family, solute carrier family 22 (organic cation transporter), member 4/5
K14156  choline/ethanolamine kinase [EC:]
K08268  hypoxia-inducible factor 1 alpha
K04448  transcription factor AP-1
K04379  proto-oncogene protein c-fos
K00968  choline-phosphate cytidylyltransferase [EC:]
K00994  diacylglycerol cholinephosphotransferase [EC:]
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:]
K01080  phosphatidate phosphatase [EC:]
K00901  diacylglycerol kinase (ATP) [EC:]
K02677  classical protein kinase C alpha type [EC:]
K19662  classical protein kinase C beta type [EC:]
K19663  classical protein kinase C gamma type [EC:]
K06128  lysophospholipase I [EC:]
K18695  glycerophosphocholine phosphodiesterase GPCPD1 [EC:]
C00093  sn-Glycerol 3-phosphate
C00114  Choline
C00157  Phosphatidylcholine
C00162  Fatty acid
C00165  Diacylglycerol
C00307  CDP-choline
C00416  Phosphatidate
C00588  Choline phosphate
C00670  sn-Glycero-3-phosphocholine
C04230  1-Acyl-sn-glycero-3-phosphocholine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Glunde K, Bhujwalla ZM, Ronen SM
Choline metabolism in malignant transformation.
Nat Rev Cancer 11:835-48 (2011)
Beloueche-Babari M, Chung YL, Al-Saffar NM, Falck-Miniotis M, Leach MO
Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy.
Br J Cancer 102:1-7 (2010)
Abalsamo L, Spadaro F, Bozzuto G, Paris L, Cecchetti S, Lugini L, Iorio E, Molinari A, Ramoni C, Podo F
Inhibition of phosphatidylcholine-specific phospholipase C results in loss of mesenchymal traits in metastatic breast cancer cells.
Breast Cancer Res 14:R50 (2012)
Foster DA
Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells.
Biochim Biophys Acta 1791:949-55 (2009)
Beloueche-Babari M, Jackson LE, Al-Saffar NM, Eccles SA, Raynaud FI, Workman P, Leach MO, Ronen SM
Identification of magnetic resonance detectable metabolic changes associated with inhibition of phosphoinositide 3-kinase signaling in human breast cancer cells.
Mol Cancer Ther 5:187-96 (2006)
Ridgway ND
The role of phosphatidylcholine and choline metabolites to cell proliferation and survival.
Crit Rev Biochem Mol Biol 48:20-38 (2013)
Awwad HM, Geisel J, Obeid R
The role of choline in prostate cancer.
Clin Biochem 45:1548-53 (2012)
Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D'Ascenzo S, Millimaggi D, Pavan A, Dolo V, Canevari S, Podo F
Alterations of choline phospholipid metabolism in ovarian tumor progression.
Cancer Res 65:9369-76 (2005)
Ackerstaff E, Glunde K, Bhujwalla ZM
Choline phospholipid metabolism: a target in cancer cells?
J Cell Biochem 90:525-33 (2003)
Park JB, Lee CS, Jang JH, Ghim J, Kim YJ, You S, Hwang D, Suh PG, Ryu SH
Phospholipase signalling networks in cancer.
Nat Rev Cancer 12:782-92 (2012)
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
Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling.
Oncogene 29:139-49 (2010)
Glunde K, Jiang L, Moestue SA, Gribbestad IS
MRS and MRSI guidance in molecular medicine: targeting and monitoring of choline and glucose metabolism in cancer.
NMR Biomed 24:673-90 (2011)
Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, Armstrong MD, Arteaga CL, Lindsley CW, Brown HA
Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.
Nat Chem Biol 5:108-17 (2009)
Foster DA, Xu L
Phospholipase D in cell proliferation and cancer.
Mol Cancer Res 1:789-800 (2003)
Zhou H, Huang S
mTOR signaling in cancer cell motility and tumor metastasis.
Crit Rev Eukaryot Gene Expr 20:1-16 (2010)
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