Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 03 2022
16 03 2022
Historique:
received:
17
03
2021
accepted:
04
03
2022
entrez:
17
3
2022
pubmed:
18
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation.
Identifiants
pubmed: 35296731
doi: 10.1038/s41598-022-08445-0
pii: 10.1038/s41598-022-08445-0
pmc: PMC8927345
doi:
Substances chimiques
Inositol
4L6452S749
N-Acetylglucosaminyltransferases
EC 2.4.1.-
Receptor, IGF Type 1
EC 2.7.10.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Acetylglucosamine
V956696549
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4464Informations de copyright
© 2022. The Author(s).
Références
Nat Rev Cancer. 2009 Aug;9(8):550-62
pubmed: 19629070
Nat Rev Drug Discov. 2002 Oct;1(10):769-83
pubmed: 12360255
Biotechnol Appl Biochem. 2016 Nov;63(6):841-851
pubmed: 26333304
Front Endocrinol (Lausanne). 2019 May 08;10:289
pubmed: 31139149
Br J Cancer. 2008 Oct 7;99(7):1096-102
pubmed: 18781172
Virology. 2009 Jan 5;383(1):78-85
pubmed: 19007961
PLoS One. 2013;8(3):e58540
pubmed: 23520519
Cancer Res. 2007 Mar 15;67(6):2420-4
pubmed: 17347513
Mol Cells. 2017 Jul 31;40(7):476-484
pubmed: 28681591
Science. 2009 Jul 10;325(5937):201-4
pubmed: 19590001
Mol Cell Biochem. 2001 May;221(1-2):147-54
pubmed: 11506178
Int J Mol Sci. 2015 Sep 22;16(9):22856-69
pubmed: 26402673
J Biol Chem. 1997 Jan 17;272(3):1639-45
pubmed: 8999839
Biochem Biophys Res Commun. 2010 Jan 29;392(1):83-8
pubmed: 20059965
Oncol Rep. 2015 Dec;34(6):3140-6
pubmed: 26397041
Cancer Res. 2000 Feb 1;60(3):760-5
pubmed: 10676665
PLoS One. 2014 Nov 14;9(11):e112580
pubmed: 25396735
PLoS One. 2012;7(7):e41992
pubmed: 22848683
PLoS One. 2014 Mar 19;9(3):e92737
pubmed: 24647478
EMBO Rep. 2003 Mar;4(3):313-9
pubmed: 12634852
J Mol Cell Biol. 2015 Apr;7(2):180-3
pubmed: 25670814
Drug Discov Today. 2005 Aug 1;10(15):1041-7
pubmed: 16055020
Biochem Pharmacol. 2008 Oct 1;76(7):873-83
pubmed: 18718450
Mol Med Rep. 2019 Jun;19(6):4529-4535
pubmed: 30942405
J Biol Chem. 1993 Dec 5;268(34):25455-62
pubmed: 8244979
Curr Protoc Mol Biol. 2010 Jul;Chapter 18:Unit 18.16
pubmed: 20583096
Trends Biochem Sci. 2010 Aug;35(8):442-9
pubmed: 20381358
PLoS One. 2013 Jun 12;8(6):e66555
pubmed: 23776686
Breast Cancer Res. 2007;9(6):R91
pubmed: 18162139
PLoS One. 2013 Jul 11;8(7):e69150
pubmed: 23935944
J Immunol. 2020 Nov 1;205(9):2499-2510
pubmed: 32978282
Mol Carcinog. 2019 Jun;58(6):1046-1055
pubmed: 30790354
Nat Struct Biol. 2001 Dec;8(12):1058-63
pubmed: 11694888
Oncol Rep. 2014 Dec;32(6):2295-306
pubmed: 25333772
FASEB J. 2013 Sep;27(9):3478-86
pubmed: 23689613
Lancet. 2019 Jan 12;393(10167):169-182
pubmed: 30638582
Cell Mol Life Sci. 2014 Jul;71(13):2403-27
pubmed: 24276851
Eur J Biochem. 1998 Nov 15;258(1):271-6
pubmed: 9851716
Folia Histochem Cytobiol. 2012 Oct 08;50(3):398-406
pubmed: 23042270
Expert Opin Ther Targets. 2013 Mar;17(3):307-20
pubmed: 23294364
Nature. 2009 Apr 9;458(7239):725-31
pubmed: 19279572
J Biol Chem. 1996 Aug 16;271(33):19810-6
pubmed: 8702689
Biochem J. 1997 Oct 1;327 ( Pt 1):139-45
pubmed: 9355745
Mol Cell Biol. 2002 Apr;22(7):1998-2010
pubmed: 11884589
Expert Opin Ther Targets. 2007 Apr;11(4):541-56
pubmed: 17373883
PLoS Pathog. 2017 Jul 24;13(7):e1006518
pubmed: 28742148
PLoS One. 2012;7(9):e46518
pubmed: 23029544
Mol Pharmacol. 2005 Apr;67(4):1206-13
pubmed: 15630078
Trends Endocrinol Metab. 2008 Dec;19(10):380-9
pubmed: 18929495
Oncotarget. 2016 Jun 28;7(26):40594-40620
pubmed: 27259240
Oncogene. 2005 Nov 24;24(53):7830-8
pubmed: 16044149
Am J Cancer Res. 2017 Jun 01;7(6):1337-1349
pubmed: 28670495
Biochem Pharmacol. 2002 Sep;64(5-6):813-7
pubmed: 12213574
Gynecol Oncol. 2016 Feb;140(2):333-44
pubmed: 26432040
Arch Med Res. 2014 Oct;45(7):525-39
pubmed: 25450584
Oncotarget. 2017 Dec 21;9(4):4625-4636
pubmed: 29435130
J Biol Chem. 2013 Aug 23;288(34):24923-34
pubmed: 23814047
Arch Physiol Biochem. 2016;122(2):54-60
pubmed: 26707268
Carcinogenesis. 1997 Jun;18(6):1183-8
pubmed: 9214601
Mol Pharmacol. 2006 Nov;70(5):1802-11
pubmed: 16926280
Cell Physiol Biochem. 2007;20(5):319-28
pubmed: 17762161
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):9333-8
pubmed: 27482104
Nature. 2008 Feb 21;451(7181):964-9
pubmed: 18288188
Mol Pharmacol. 2005 Sep;68(3):885-94
pubmed: 15976035
Carcinogenesis. 2006 May;27(5):962-71
pubmed: 16400188
Front Endocrinol (Lausanne). 2018 Oct 09;9:602
pubmed: 30356686
Oncotarget. 2016 Jul 12;7(28):44596-44607
pubmed: 27331873
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1834-9
pubmed: 14766979
Oncol Rep. 2011 Sep;26(3):743-9
pubmed: 21637923
Biochem Biophys Res Commun. 2017 Feb 5;483(2):793-802
pubmed: 27845045
Int J Cancer. 2006 Apr 15;118(8):1877-83
pubmed: 16287065
FASEB J. 2014 Feb;28(2):1010-21
pubmed: 24174424
Front Endocrinol (Lausanne). 2013 Aug 12;4:99
pubmed: 23964270