title: O-GlcNAcylation: A New Cancer Hallmark?
abstract: O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by O-GlcNAc-transferase (OGT) and removed by O-GlcNAcase, this dynamic modification is dependent on environmental glucose concentration. O-GlcNAcylation regulates the activities of a wide panel of proteins involved in almost all aspects of cell biology. As a nutrient sensor, O-GlcNAcylation can relay the effects of excessive nutritional intake, an important cancer risk factor, on protein activities and cellular functions. Indeed, O-GlcNAcylation has been shown to play a significant role in cancer development through different mechanisms. O-GlcNAcylation and OGT levels are increased in different cancers (breast, prostate, colon…) and vary during cell cycle progression. Modulating their expression or activity can alter cancer cell proliferation and/or invasion. Interestingly, major oncogenic factors have been shown to be directly O-GlcNAcylated (p53, MYC, NFκB, β-catenin…). Furthermore, chromatin dynamics is modulated by O-GlcNAc. DNA methylation enzymes of the Tet family, involved epigenetic alterations associated with cancer, were recently found to interact with and target OGT to multi-molecular chromatin-remodeling complexes. Consistently, histones are subjected to O-GlcNAc modifications which regulate their function. Increasing number of evidences point out the central involvement of O-GlcNAcylation in tumorigenesis, justifying the attention received as a potential new approach for cancer treatment. However, comprehension of the underlying mechanism remains at its beginnings. Future challenge will be to address directly the role of O-GlcNAc-modified residues in oncogenic-related proteins to eventually propose novel strategies to alter cancer development and/or progression.
authors: Institut Cochin, Université Paris Descartes, CNRS (UMR8104) , Paris , France ; INSERM, U1016 , Paris , France.
authors: Yann
authors: Y
authors: Fardini
authors: Vanessa
authors: V
authors: Dehennaut
authors: Tony
authors: T
authors: Lefebvre
authors: Tarik
authors: T
authors: Issad
keywords: O-GlcNAc; O-glycosylation; cancer; cell cycle; epigenetics; metastasis; post-translational modification; transcription factors
references: Diabetes Metab. 2010 Jun;36(3):182-91
references: 20554237
references: Science. 2009 Jul 10;325(5937):201-4
references: 19590001
references: Oncogenesis. 2012 Dec 10;1:e36
references: 23552487
references: Nat Rev Cancer. 2011 Sep 23;11(10):726-34
references: 21941284
references: Nature. 2009 Nov 5;462(7269):104-7
references: 19847165
references: Trends Endocrinol Metab. 2013 Jun;24(6):301-9
references: 23647930
references: J Biol Chem. 2012 Mar 30;287(14):11070-81
references: 22275356
references: Differentiation. 2001 Dec;69(1):1-17
references: 11776390
references: Leukemia. 2010 Sep;24(9):1588-98
references: 20668475
references: J Biol Chem. 2011 Oct 28;286(43):37483-95
references: 21896475
references: Annu Rev Med. 2010;61:301-16
references: 19824817
references: Cell. 2004 Aug 6;118(3):285-96
references: 15294155
references: Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1701-5
references: 2000378
references: Cancer. 2011 May 1;117(9):1788-99
references: 21509756
references: Nat Cell Biol. 2006 Oct;8(10):1074-83
references: 16964247
references: Oncogene. 2010 May 13;29(19):2831-42
references: 20190804
references: Nat Rev Cancer. 2008 Dec;8(12):976-90
references: 19029958
references: J Biol Chem. 2005 Sep 23;280(38):32944-56
references: 16027160
references: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4417-21
references: 7753821
references: PLoS One. 2012;7(7):e41992
references: 22848683
references: J Cell Sci. 2012 Nov 15;125(Pt 22):5578-86
references: 22899716
references: World J Gastroenterol. 2009 Nov 7;15(41):5141-8
references: 19891012
references: Nature. 2003 Feb 6;421(6923):639-43
references: 12571598
references: Biochimie. 2008 May;90(5):679-85
references: 18359296
references: Nat Rev Cancer. 2009 Aug;9(8):550-62
references: 19629070
references: Exp Cell Res. 2013 Jun 10;319(10):1482-90
references: 23524144
references: Adv Exp Med Biol. 2001;491:413-8
references: 14533811
references: Maturitas. 2008 May 20;60(1):19-30
references: 18485631
references: Endocrinology. 1995 Jul;136(7):2809-16
references: 7789306
references: FEBS Lett. 2008 Mar 5;582(5):829-34
references: 18280254
references: J Biol Chem. 2012 Apr 6;287(15):12195-203
references: 22371497
references: Biochim Biophys Acta. 2012 Jan;1819(1):28-37
references: 21978825
references: Mol Cell. 2013 Feb 21;49(4):645-56
references: 23352454
references: J Exp Zool. 1971 Jun;177(2):129-45
references: 5106340
references: J Cell Biochem. 2008 Nov 1;105(4):956-64
references: 18821585
references: Best Pract Res Clin Endocrinol Metab. 2008 Aug;22(4):551-71
references: 18971118
references: Nat Cell Biol. 2011 Aug 28;13(10):1272-9
references: 21968997
references: Nature. 2013 Jan 24;493(7433):561-4
references: 23222540
references: Biochem Biophys Res Commun. 2008 May 2;369(2):539-46
references: 18298951
references: Amino Acids. 2011 Mar;40(3):781-92
references: 20640461
references: Nat Rev Cancer. 2012 Jan 19;12(2):121-32
references: 22257950
references: J Am Chem Soc. 2004 Sep 1;126(34):10500-1
references: 15327282
references: J Biol Chem. 2013 May 24;288(21):15121-30
references: 23592772
references: Eur J Biochem. 2004 Oct;271(19):3843-54
references: 15373830
references: Breast Cancer Res. 2007;9(6):R91
references: 18162139
references: Biochim Biophys Acta. 2010 Feb;1800(2):67-79
references: 19732809
references: Nat Rev Cancer. 2004 Aug;4(8):579-91
references: 15286738
references: Ann N Y Acad Sci. 2007 Oct;1114:434-55
references: 17986602
references: PLoS One. 2013 Jul 11;8(7):e69150
references: 23935944
references: Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17345-50
references: 18988733
references: Cancer Cell. 2007 Oct;12(4):303-12
references: 17936556
references: Chembiochem. 2006 Jan;7(1):88-97
references: 16345111
references: EMBO J. 2010 Nov 17;29(22):3787-96
references: 20959806
references: Biochim Biophys Acta. 2012 Dec;1820(12):1839-48
references: 22967762
references: EMBO J. 2013 Mar 6;32(5):612-3
references: 23403924
references: FASEB J. 2013 Sep;27(9):3478-86
references: 23689613
references: Cell. 2013 Mar 14;152(6):1237-51
references: 23498934
references: Nat Cell Biol. 2008 May;10(5):611-8
references: 18391940
references: J Biol Chem. 2010 Nov 5;285(45):34460-8
references: 20805223
references: Am J Physiol Endocrinol Metab. 2012 Feb 15;302(4):E417-24
references: 22114026
references: Med Oncol. 2012 Jun;29(2):985-93
references: 21461968
references: Glycobiology. 2012 Jun;22(6):839-48
references: 22322011
references: Clin Exp Med. 2012 Mar;12(1):61-5
references: 21567137
references: Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a001107
references: 20182618
references: J Biol Chem. 2007 Apr 27;282(17):12527-36
references: 17329255
references: J Biol Chem. 1997 Mar 28;272(13):8752-8
references: 9079710
references: Oncol Rep. 2012 Aug;28(2):494-500
references: 22664592
references: Mol Biol Cell. 2008 Oct;19(10):4130-40
references: 18653473
references: Nature. 2009 Apr 9;458(7239):725-31
references: 19279572
references: PLoS One. 2012;7(9):e46518
references: 23029544
references: Biochim Biophys Acta. 2011 Apr;1812(4):514-9
references: 21255644
references: J Biol Chem. 2001 Jul 13;276(28):26656-65
references: 11350965
references: Nature. 2009 May 21;459(7245):455-9
references: 19377461
references: Trends Cell Biol. 2012 Nov;22(11):557-66
references: 22995730
references: Biochim Biophys Acta. 2010 May-Jun;1799(5-6):353-64
references: 20202486
references: Trends Endocrinol Metab. 2008 Dec;19(10):380-9
references: 18929495
references: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19915-20
references: 21045127
references: Diabetes Metab. 2010 Dec;36(6 Pt 1):423-35
references: 21074472
references: Cancer Res. 2013 Aug 15;73(16):5277-87
references: 23720054
references: EMBO J. 2001 Apr 2;20(7):1630-9
references: 11285227
references: Curr Opin Genet Dev. 2008 Feb;18(1):54-61
references: 18387799
references: Clin Cancer Res. 2006 Mar 1;12(5):1447-53
references: 16533767
references: Int J Mol Med. 2010 Apr;25(4):643-8
references: 20198314
references: FEBS J. 2011 Jan;278(1):16-27
references: 21087457
references: Nat Rev Cancer. 2011 Aug 18;11(9):678-84
references: 21850036
references: Nature. 2007 Apr 26;446(7139):1017-22
references: 17460662
references: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3431-6
references: 19202066
references: J Biol Chem. 1995 Aug 11;270(32):18961-5
references: 7642555
references: Annu Rev Med. 2003;54:131-52
references: 12525670
references: Trends Biochem Sci. 2010 Oct;35(10):547-55
references: 20466550
references: Cancer Cell. 2013 May 13;23(5):634-46
references: 23680148
references: EMBO J. 2013 Mar 6;32(5):645-55
references: 23353889
references: Nat Rev Mol Cell Biol. 2012 Apr 23;13(5):312-21
references: 22522719
references: Genes Cells. 2002 Jan;7(1):11-7
references: 11856369
references: J Pathol. 2005 Jan;205(1):21-8
references: 15586368
references: J Biol Chem. 2008 Aug 1;283(31):21411-7
references: 18519567
references: Biochem J. 2008 Dec 1;416(2):211-8
references: 18823284
references: J Biol Chem. 2008 May 9;283(19):13009-20
references: 18353774
references: J Am Coll Nutr. 2009 Aug;28 Suppl:500S-516S
references: 20234038
references: Carcinogenesis. 1997 Jun;18(6):1183-8
references: 9214601
references: Mol Cell Proteomics. 2008 Nov;7(11):2229-45
references: 18617508
references: J Biol Chem. 2003 Dec 19;278(51):51606-12
references: 14563837
references: Aging Cell. 2012 Jun;11(3):439-48
references: 22314054
references: Trends Mol Med. 2010 Nov;16(11):528-36
references: 20932800
references: FASEB J. 2001 Sep;15(11):1865-76
references: 11532966
references: Biochim Biophys Acta. 2002 Nov 14;1573(2):121-9
references: 12399021
references: EMBO J. 2012 Jun 13;31(12):2714-36
references: 22617422
references: Nature. 2008 Feb 21;451(7181):964-9
references: 18288188
references: Chem Biol. 2006 Sep;13(9):937-44
references: 16984883
references: Oncogene. 2009 Mar 5;28(9):1280-4
references: 19151750
references: Exp Cell Res. 2001 Feb 15;263(2):243-53
references: 11161723
references: Nature. 2011 Nov 27;480(7378):557-60
references: 22121020
references: Cancer. 2008 Nov 1;113(9):2385-97
references: 18819158
references: Glycoconj J. 2009 Apr;26(3):301-11
references: 18633701
references: Annu Rev Biochem. 2011;80:825-58
references: 21391816
references: Cancer Res. 2010 Aug 1;70(15):6344-51
references: 20610629
references: Mol Cell Biol. 2002 Feb;22(3):874-85
references: 11784863
references: Proteomics Clin Appl. 2013 Oct;7(9-10):597-606
references: 23640805
references: Clin Lab. 2012;58(5-6):579-83
references: 22783592
references: Nature. 2007 May 24;447(7143):407-12
references: 17522673
references: Science. 2012 Aug 24;337(6097):975-80
references: 22923583
references: Science. 2011 Sep 2;333(6047):1300-3
references: 21778364
references: Ginekol Pol. 2012 Jan;83(1):22-6
references: 22384635
references: J Clin Endocrinol Metab. 2012 Jul;97(7):2347-53
references: 22523334
references: Proteomics. 2013 Jul;13(14):2088-99
references: 23576270
references: J Biol Chem. 1997 Jan 24;272(4):2421-8
references: 8999954
references: Biochim Biophys Acta. 2001 Sep 28;1537(2):147-57
references: 11566258