KEGG PATHWAY: map05231

PATHWAY: map05231

Entry

map05231                    Pathway

Name

Choline metabolism in cancer

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: overview

Pathway map

map05231

Choline metabolism in cancer

Reference

PMID:22089420

Authors

Glunde K, Bhujwalla ZM, Ronen SM

Title

Choline metabolism in malignant transformation.

Journal

Nat Rev Cancer 11:835-48 (2011)
DOI:10.1038/nrc3162

Reference

PMID:19935796

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

Br J Cancer 102:1-7 (2010)
DOI:10.1038/sj.bjc.6605457

Reference

PMID:22429397

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

Breast Cancer Res 14:R50 (2012)
DOI:10.1186/bcr3151

Reference

PMID:19264150

Authors

Foster DA

Title

Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells.

Journal

Biochim Biophys Acta 1791:949-55 (2009)
DOI:10.1016/j.bbalip.2009.02.009

Reference

PMID:16432178

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

Mol Cancer Ther 5:187-96 (2006)
DOI:10.1158/1535-7163.MCT-03-0220

Reference

PMID:23350810

Authors

Ridgway ND

Title

The role of phosphatidylcholine and choline metabolites to cell proliferation and survival.

Journal

Crit Rev Biochem Mol Biol 48:20-38 (2013)
DOI:10.3109/10409238.2012.735643

Reference

PMID:22921309

Authors

Awwad HM, Geisel J, Obeid R

Title

The role of choline in prostate cancer.

Journal

Clin Biochem 45:1548-53 (2012)
DOI:10.1016/j.clinbiochem.2012.08.012

Reference

PMID:16230400

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

Cancer Res 65:9369-76 (2005)
DOI:10.1158/0008-5472.CAN-05-1146

Reference

PMID:14523987

Authors

Ackerstaff E, Glunde K, Bhujwalla ZM

Title

Choline phospholipid metabolism: a target in cancer cells?

Journal

J Cell Biochem 90:525-33 (2003)
DOI:10.1002/jcb.10659

Reference

PMID:23076158

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

Nat Rev Cancer 12:782-92 (2012)
DOI:10.1038/nrc3379

Reference

PMID:19855431

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

Oncogene 29:139-49 (2010)
DOI:10.1038/onc.2009.317

Reference

PMID:21793073

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

NMR Biomed 24:673-90 (2011)
DOI:10.1002/nbm.1751

Reference

PMID:19136975

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

Nat Chem Biol 5:108-17 (2009)
DOI:10.1038/nchembio.140

Reference

PMID:14517341

Authors

Foster DA, Xu L

Title

Phospholipase D in cell proliferation and cancer.

Journal

Mol Cancer Res 1:789-800 (2003)

Reference

PMID:20528734

Authors

Zhou H, Huang S

Title

mTOR signaling in cancer cell motility and tumor metastasis.

Journal

Crit Rev Eukaryot Gene Expr 20:1-16 (2010)
DOI:10.1615/critreveukargeneexpr.v20.i1.10

Related
pathway

map00564

Glycerophospholipid metabolism

map04010

MAPK signaling pathway

map04150

mTOR signaling pathway

map04151

PI3K-Akt signaling pathway

map04810

Regulation of actin cytoskeleton

KO pathway

ko05231

All links

Chemical substance (11)   
   KEGG COMPOUND (11)   
Gene (154708)   
   KEGG ORTHOLOGY (61)   
   RefGene (154647)   
Literature (15)   
   PubMed (15)   
All databases (154734)   

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