title: Choline metabolism in malignant transformation.
abstract: Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy.
authors.affiliation: The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, 720 Rutland Avenue, Baltimore, MD 21205, USA. kglunde@mri.jhu.edu
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
authors.forename: Sabrina M
authors.initials: SM
authors.lastname: Ronen
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002794:Choline / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D015398:Signal Transduction
chemical_list: D002794:Choline
references.citation: J Biol Chem. 1956 Sep;222(1):193-214
references.pmid: 13366993
references.citation: Oncol Res. 2003;14(1):31-7
references.pmid: 14552589
references.citation: Int J Cancer. 1997 Mar 4;70(5):567-74
references.pmid: 9052757
references.citation: J Am Chem Soc. 2008 Apr 9;130(14):4598-9
references.pmid: 18345678
references.citation: J Biol Chem. 1948 Jan;172(1):191-8
references.pmid: 18920784
references.citation: Magn Reson Med. 2008 Jul;60(1):33-40
references.pmid: 18581409
references.citation: Cell. 1990 Jun 15;61(6):1113-20
references.pmid: 2112426
references.citation: J Invest Dermatol. 2003 Jul;121(1):69-76
references.pmid: 12839565
references.citation: J Biol Chem. 1957 Aug;227(2):951-62
references.pmid: 13463016
references.citation: J Biol Chem. 1989 Oct 5;264(28):16638-43
references.pmid: 2506180
references.citation: Mol Cancer Ther. 2006 Jan;5(1):187-96
references.pmid: 16432178
references.citation: Cancer Res. 2002 Feb 1;62(3):688-95
references.pmid: 11830521
references.citation: Semin Nucl Med. 2011 Jul;41(4):265-82
references.pmid: 21624561
references.citation: Oncogene. 2003 Jun 19;22(25):3937-42
references.pmid: 12813467
references.citation: Magn Reson Med. 1993 Nov;30(5):525-33
references.pmid: 8259052
references.citation: Cancer Res. 2010 Mar 15;70(6):2274-84
references.pmid: 20197462
references.citation: Arch Biochem Biophys. 2006 Mar 1;447(1):23-33
references.pmid: 16466687
references.citation: Biochem J. 1991 Oct 15;279 ( Pt 2):559-65
references.pmid: 1659382
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Cancer Res. 2005 Apr 15;65(8):3356-63
references.pmid: 15833869
references.citation: Breast Cancer Res. 2010;12(5):R84
references.pmid: 20946630
references.citation: Semin Oncol. 2011 Feb;38(1):26-41
references.pmid: 21362514
references.citation: Mol Cancer. 2009 Dec 31;8:131
references.pmid: 20042122
references.citation: NMR Biomed. 2011 Apr;24(3):316-24
references.pmid: 20862660
references.citation: Anticancer Res. 1999 May-Jun;19(3A):1737-46
references.pmid: 10470108
references.citation: J Biol Chem. 2001 Aug 3;276(31):28976-83
references.pmid: 11390384
references.citation: Cancer Res. 2005 Jul 1;65(13):5647-53
references.pmid: 15994937
references.citation: J Biol Chem. 1999 Jan 8;274(2):735-8
references.pmid: 9873009
references.citation: Oncogene. 2002 Jun 20;21(27):4317-22
references.pmid: 12082619
references.citation: J Biol Chem. 2005 Jan 14;280(2):853-6
references.pmid: 15536089
references.citation: Cancer Res. 2010 Nov 15;70(22):9012-21
references.pmid: 21045154
references.citation: Cell Biol Int. 1997 Jun;21(6):375-81
references.pmid: 9268491
references.citation: Neoplasia. 2006 Sep;8(9):758-71
references.pmid: 16984733
references.citation: Neoplasia. 2009 May;11(5):477-84
references.pmid: 19412432
references.citation: NMR Biomed. 1998 Nov;11(7):354-9
references.pmid: 9859941
references.citation: Radiology. 1989 Aug;172(2):541-8
references.pmid: 2748837
references.citation: Oncotarget. 2010 Jul;1(3):185-97
references.pmid: 21037799
references.citation: Biochim Biophys Acta. 1994 Apr 14;1212(1):26-42
references.pmid: 8155724
references.citation: Proc Natl Acad Sci U S A. 1986 Sep;83(18):6785-9
references.pmid: 3462727
references.citation: Lancet. 1983 Jun 25;1(8339):1435-6
references.pmid: 6134191
references.citation: Neurosurgery. 1993 Mar;32(3):485-9; discussion 489-90
references.pmid: 8384328
references.citation: Cancer Res. 1999 Jan 1;59(1):80-4
references.pmid: 9892190
references.citation: Mol Cancer Ther. 2002 Sep;1(11):885-92
references.pmid: 12481409
references.citation: Cancer Res. 2009 Apr 15;69(8):3464-71
references.pmid: 19336572
references.citation: Prog Lipid Res. 2004 May;43(3):266-81
references.pmid: 15003397
references.citation: J Biol Chem. 1985 May 25;260(10):6006-11
references.pmid: 2987212
references.citation: Exp Cell Res. 2004 Oct 1;299(2):370-82
references.pmid: 15350536
references.citation: Proc Natl Acad Sci U S A. 1977 Jan;74(1):87-91
references.pmid: 13372
references.citation: Mol Pharm. 2010 Dec 6;7(6):2077-92
references.pmid: 20698576
references.citation: Cancer Res. 2004 Sep 15;64(18):6732-9
references.pmid: 15374991
references.citation: Technol Cancer Res Treat. 2007 Oct;6(5):375-82
references.pmid: 17877425
references.citation: NMR Biomed. 1997 Jan;10(1):2-12
references.pmid: 9251109
references.citation: FEBS Lett. 2002 Oct 30;531(1):58-61
references.pmid: 12401203
references.citation: Cancer Res. 1990 Jul 15;50(14):4177-89
references.pmid: 2194650
references.citation: Cancer Res. 2010 Mar 1;70(5):2126-35
references.pmid: 20179205
references.citation: Cancer Chemother Pharmacol. 1999;44 Suppl:S29-30
references.pmid: 10602908
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1638-42
references.pmid: 15668389
references.citation: Biochem Biophys Res Commun. 2002 Aug 23;296(3):580-3
references.pmid: 12176020
references.citation: Cancer Res. 2010 Jul 1;70(13):5507-17
references.pmid: 20551061
references.citation: Radiology. 2009 Jun;251(3):653-62
references.pmid: 19276320
references.citation: Mol Cancer Res. 2003 Sep;1(11):789-800
references.pmid: 14517341
references.citation: ACS Nano. 2010 Nov 23;4(11):6707-16
references.pmid: 20958072
references.citation: Invest Radiol. 2011 Jan;46(1):25-33
references.pmid: 21188832
references.citation: Neuro Oncol. 2010 Jun;12(6):559-69
references.pmid: 20156803
references.citation: Nat Neurosci. 2000 Feb;3(2):120-5
references.pmid: 10649566
references.citation: Cancer Res. 2005 Dec 1;65(23):11034-43
references.pmid: 16322253
references.citation: Oncol Rep. 2007 Nov;18(5):1329-34
references.pmid: 17914593
references.citation: J Natl Cancer Inst. 2003 Nov 5;95(21):1624-33
references.pmid: 14600095
references.citation: Prog Lipid Res. 2008 May;47(3):204-20
references.pmid: 18295604
references.citation: Biochem J. 1994 Jan 1;297 ( Pt 1):241-7
references.pmid: 8280105
references.citation: Oncogene. 2009 Jul 9;28(27):2485-91
references.pmid: 19448666
references.citation: J Biol Chem. 2006 Feb 24;281(8):4938-48
references.pmid: 16371353
references.citation: Int J Oncol. 2002 Sep;21(3):477-85
references.pmid: 12168089
references.citation: Cancer Lett. 2000 Dec 20;161(2):207-14
references.pmid: 11090971
references.citation: NMR Biomed. 2010 Apr;23(3):233-41
references.pmid: 20175134
references.citation: J Biol Chem. 1997 Feb 7;272(6):3860-8
references.pmid: 9013646
references.citation: J Neurochem. 1994 Oct;63(4):1538-43
references.pmid: 7931308
references.citation: Biochem J. 2002 May 1;363(Pt 3):777-84
references.pmid: 11964179
references.citation: Biochem Biophys Res Commun. 2003 Mar 14;302(3):615-9
references.pmid: 12615079
references.citation: NMR Biomed. 1992 Sep-Oct;5(5):303-24
references.pmid: 1333263
references.citation: Mol Imaging. 2003 Apr;2(2):124-30
references.pmid: 12964309
references.citation: Cancer Res. 2004 Jun 15;64(12):4270-6
references.pmid: 15205341
references.citation: Mol Imaging. 2004 Oct;3(4):319-23
references.pmid: 15802048
references.citation: J Biol Chem. 1996 Apr 26;271(17):9955-61
references.pmid: 8626633
references.citation: Mol Cancer Ther. 2006 May;5(5):1325-34
references.pmid: 16731766
references.citation: Arch Biochem Biophys. 2009 Mar 1;483(1):90-8
references.pmid: 19135976
references.citation: Oncogene. 2001 Mar 1;20(9):1110-7
references.pmid: 11314048
references.citation: J Biol Chem. 2007 May 18;282(20):14827-35
references.pmid: 17384411
references.citation: Biochem Biophys Res Commun. 2000 Nov 11;278(1):140-3
references.pmid: 11185526
references.citation: Mol Cancer Ther. 2008 Aug;7(8):2556-65
references.pmid: 18723500
references.citation: Cancer Res. 2006 Jan 1;66(1):427-34
references.pmid: 16397258
references.citation: Contrast Media Mol Imaging. 2011 May-Jun;6(3):139-47
references.pmid: 21698772
references.citation: Neuroimaging Clin N Am. 2010 Aug;20(3):293-310
references.pmid: 20708548
references.citation: J Biol Chem. 1987 Nov 5;262(31):14875-8
references.pmid: 3667610
references.citation: NMR Biomed. 2011 Jul;24(6):648-72
references.pmid: 21387442
references.citation: J Biol Chem. 2003 Apr 25;278(17):14753-61
references.pmid: 12584202
references.citation: Oncogene. 2003 Dec 4;22(55):8803-12
references.pmid: 14654777
references.citation: Nature. 1987 Nov 19-25;330(6145):269-72
references.pmid: 3313065
references.citation: Breast Cancer Res. 2010;12(3):R27
references.pmid: 20462431
references.citation: Nagoya J Med Sci. 2009 Sep;71(3-4):127-36
references.pmid: 19994725
references.citation: Cancer Res. 2007 Dec 1;67(23):11284-90
references.pmid: 18056454
references.citation: Magn Reson Med. 1995 Mar;33(3):422-6
references.pmid: 7760711
references.citation: Oncogene. 2002 Jan 31;21(6):937-46
references.pmid: 11840339
references.citation: Anticancer Res. 1996 May-Jun;16(3B):1375-80
references.pmid: 8694504
references.citation: Neuromolecular Med. 2010 Dec;12(4):320-30
references.pmid: 20552297
references.citation: Mol Pharmacol. 2002 Oct;62(4):911-20
references.pmid: 12237338
references.citation: Oncogene. 2004 Oct 28;23(50):8247-59
references.pmid: 15378008
references.citation: Acta Biochim Biophys Sin (Shanghai). 2007 Sep;39(9):668-74
references.pmid: 17805461
references.citation: Biochim Biophys Acta. 2007 Sep;1771(9):1148-55
references.pmid: 17728180
references.citation: NMR Biomed. 2009 Jan;22(1):114-27
references.pmid: 19016452
references.citation: Eur J Biochem. 2002 Sep;269(18):4649-55
references.pmid: 12230578
references.citation: Biochim Biophys Acta. 1997 Sep 4;1348(1-2):79-90
references.pmid: 9370319
references.citation: Anticancer Drug Des. 1994 Aug;9(4):363-72
references.pmid: 7916902
references.citation: Mol Imaging. 2006 Oct-Dec;5(4):498-509
references.pmid: 17150162
references.citation: Mol Cell Biol. 1989 Jan;9(1):325-8
references.pmid: 2538723
references.citation: PLoS One. 2009 Nov 12;4(11):e7819
references.pmid: 19915674
references.citation: BMC Cancer. 2010 Aug 17;10:433
references.pmid: 20716336
references.citation: Oncogene. 1994 May;9(5):1387-95
references.pmid: 8152799
references.citation: Oncogene. 2012 Mar 15;31(11):1431-41
references.pmid: 21822308
references.citation: J Magn Reson Imaging. 2002 Oct;16(4):430-50
references.pmid: 12353258
references.citation: Cancer Lett. 1987 Jun;35(3):237-44
references.pmid: 3594421
references.citation: J Magn Reson. 1998 Nov;135(1):194-202
references.pmid: 9799694
references.citation: Biochim Biophys Acta. 1999 Jul 30;1439(2):245-63
references.pmid: 10425399
references.citation: Int J Cancer. 2007 Apr 15;120(8):1721-30
references.pmid: 17236204
references.citation: J Natl Cancer Inst. 2002 Aug 21;94(16):1197-203
references.pmid: 12189222
references.citation: Cancer Res. 2010 May 15;70(10):4233-42
references.pmid: 20442281
references.citation: Lancet Oncol. 2007 Oct;8(10):889-97
references.pmid: 17851129
references.citation: Trends Biochem Sci. 1988 May;13(5):172-7
references.pmid: 3255199
references.citation: Magn Reson Imaging. 2011 Jan;29(1):25-31
references.pmid: 20832225
references.citation: Biochim Biophys Acta. 1998 Jun 15;1392(2-3):217-32
references.pmid: 9630635
references.citation: Nucl Med Biol. 2009 Apr;36(3):335-42
references.pmid: 19324279
references.citation: Nat Cell Biol. 2007 Jun;9(6):706-12
references.pmid: 17486115
references.citation: J Biol Chem. 1992 Apr 5;267(10):6719-24
references.pmid: 1313020
references.citation: NMR Biomed. 2006 Jun;19(4):476-83
references.pmid: 16763969
references.citation: Exp Cell Res. 2004 Jan 15;292(2):385-92
references.pmid: 14697345
references.citation: IDrugs. 2001 Apr;4(4):419-26
references.pmid: 16015482
references.citation: J Neurochem. 2005 Mar;92(5):1116-25
references.pmid: 15715662
references.citation: Biochim Biophys Acta. 2003 Jul 4;1633(1):1-12
references.pmid: 12842190
references.citation: Neuro Oncol. 2010 Nov;12(11):1152-61
references.pmid: 20647244
references.citation: J Cancer Res Clin Oncol. 1997;123(5):280-5
references.pmid: 9201251
references.citation: NMR Biomed. 2005 Nov;18(7):430-9
references.pmid: 16206237
references.citation: J Biol Chem. 2008 Jan 18;283(3):1456-1462
references.pmid: 18029352
references.citation: Jpn J Cancer Res. 1986 Dec;77(12):1201-6
references.pmid: 3029002
references.citation: Cancer Lett. 1989 Jul 15;46(2):149-52
references.pmid: 2752384
references.citation: Oncogene. 1999 Aug 19;18(33):4718-25
references.pmid: 10467419
references.citation: FASEB J. 1998 Oct;12(13):1309-17
references.pmid: 9761774
references.citation: Trends Cell Biol. 2003 Oct;13(10):540-6
references.pmid: 14507482
references.citation: J Biol Chem. 1990 Apr 15;265(11):6042-7
references.pmid: 2156839
references.citation: Cancer Res. 2008 Jan 1;68(1):172-80
references.pmid: 18172309
references.citation: Biochim Biophys Acta. 1984 Sep 14;805(1):104-16
references.pmid: 6477969
references.citation: J Proteome Res. 2010 Jan;9(1):319-32
references.pmid: 19908917
references.citation: Biochem Biophys Res Commun. 1980 May 30;94(2):690-6
references.pmid: 7396928
references.citation: Jpn J Cancer Res. 1999 Apr;90(4):419-24
references.pmid: 10363580
references.citation: Int J Cancer. 2000 Mar 15;85(6):882-8
references.pmid: 10709112
references.citation: Biochem J. 1999 Jan 1;337 ( Pt 1):23-7
references.pmid: 9854020
references.citation: Biosci Rep. 1981 Apr;1(4):319-25
references.pmid: 7295895
references.citation: Drug Dev Ind Pharm. 2002 Aug;28(7):749-71
references.pmid: 12236062
references.citation: J Biol Chem. 1995 Sep 8;270(36):21299-306
references.pmid: 7673165
references.citation: Oncogene. 1993 Nov;8(11):2959-68
references.pmid: 8414498
references.citation: J Biol Chem. 2001 Jan 12;276(2):1226-32
references.pmid: 11042196
references.citation: Cancer Treat Rep. 1984 Nov;68(11):1403-5
references.pmid: 6541973
references.citation: Cancer Res. 2008 Aug 15;68(16):6541-9
references.pmid: 18701477
references.citation: FEBS Lett. 1992 Jun 15;304(2-3):229-32
references.pmid: 1618328
references.citation: Oncogene. 1997 Nov 6;15(19):2289-301
references.pmid: 9393874
references.citation: Rev Physiol Biochem Pharmacol. 2003;150:36-90
references.pmid: 12827517
references.citation: Oncogene. 2010 Jan 7;29(1):139-49
references.pmid: 19855431
references.citation: J Biol Chem. 2001 Jul 6;276(27):24645-53
references.pmid: 11323430
references.citation: Br J Cancer. 2001 Mar 2;84(5):691-6
references.pmid: 11237392
references.citation: Phys Chem Chem Phys. 2010 Jun 14;12(22):5818-23
references.pmid: 20461252
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1835-40
references.pmid: 10677542
references.citation: Int J Biochem Cell Biol. 2008;40(9):1753-63
references.pmid: 18296102
references.citation: Carcinogenesis. 2001 Oct;22(10):1641-7
references.pmid: 11577003
references.citation: Oncogene. 2009 Jul 2;28(26):2425-35
references.pmid: 19448670
references.citation: J Magn Reson Imaging. 2002 Oct;16(4):451-63
references.pmid: 12353259
references.citation: J Mol Med (Berl). 2003 Feb;81(2):126-31
references.pmid: 12601529
references.citation: Anticancer Res. 1999 Jan-Feb;19(1B):671-5
references.pmid: 10216475
references.citation: J Neurosurg. 2007 Apr;106(4):660-6
references.pmid: 17432719
references.citation: Biochem Biophys Res Commun. 2001 Dec 21;289(5):1019-24
references.pmid: 11741292
references.citation: Biochem Biophys Res Commun. 1993 Jun 15;193(2):497-503
references.pmid: 8390242
references.citation: Physiol Genomics. 2006 Jun 16;26(1):76-90
references.pmid: 16609143
references.citation: Mol Cell Biochem. 1996 Sep 20;162(2):97-103
references.pmid: 8905631
references.citation: J Biol Chem. 1953 May;202(1):431-44
references.pmid: 13061469
references.citation: Drugs Exp Clin Res. 1996;22(6):287-94
references.pmid: 9034754
references.citation: NMR Biomed. 2010 Jun;23(5):473-9
references.pmid: 20225233
references.citation: MAGMA. 1998 Aug;6(1):44-52
references.pmid: 9794289
references.citation: Trends Biochem Sci. 2000 Sep;25(9):441-7
references.pmid: 10973058