A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation.
Hippo
WNT
glioblastoma
glioma stem cells
tankyrase
temozolomide
β-catenin
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
19 Jun 2020
19 Jun 2020
Historique:
received:
31
05
2020
revised:
13
06
2020
accepted:
16
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
25
6
2020
Statut:
epublish
Résumé
Evidence suggests that the growth and therapeutic resistance of glioblastoma (GBM) may be enabled by a population of glioma stem cells (GSCs) that are regulated by typical stem cell pathways, including the WNT/β-catenin signaling pathway. We wanted to explore the effect of treating GSCs with a small-molecule inhibitor of tankyrase, G007-LK, which has been shown to be a potent modulator of the WNT/β-catenin and Hippo pathways in colon cancer. Four primary GSC cultures and two primary adult neural stem cell cultures were treated with G007-LK and subsequently evaluated through the measurement of growth characteristics, as well as the expression of WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Treatment with G007-LK decreased in vitro proliferation and sphere formation in all four primary GSC cultures in a dose-dependent manner. G007-LK treatment altered the expression of key downstream WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Finally, cotreatment with the established GBM chemotherapeutic compound temozolomide (TMZ) led to an additive reduction in sphere formation, suggesting that WNT/β-catenin signaling may contribute to TMZ resistance. These observations suggest that tankyrase inhibition may serve as a supplement to current GBM therapy, although more work is needed to determine the exact downstream mechanisms involved.
Identifiants
pubmed: 32575464
pii: cancers12061630
doi: 10.3390/cancers12061630
pmc: PMC7352564
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : The Research Council of Norway
ID : 174938, 262613 and 267639
Organisme : The Norwegian Cancer Society
ID : 09/00385-1 and 5803958
Organisme : South-Eastern Norway Regional Health Authority
ID : 16/00528-9, 15/00779-2, 2015012 and 2019090
Références
Nature. 2006 Dec 7;444(7120):756-60
pubmed: 17051156
Cancer Discov. 2019 Oct;9(10):1358-1371
pubmed: 31337618
Stem Cells Dev. 2014 Jun 15;23(12):1328-39
pubmed: 24548083
Science. 1997 Mar 21;275(5307):1787-90
pubmed: 9065402
Oncotarget. 2016 Dec 13;7(50):82686-82699
pubmed: 27764783
Cancers (Basel). 2019 Feb 01;11(2):
pubmed: 30717152
Oncol Rep. 2019 May;41(5):3080-3088
pubmed: 30864699
J Proteome Res. 2012 Oct 5;11(10):5011-21
pubmed: 22909274
Mol Cancer Res. 2018 Mar;16(3):543-553
pubmed: 29222171
Mol Cancer. 2015 Jun 17;14:121
pubmed: 26081429
J Neuropathol Exp Neurol. 2016 May;75(5):388-96
pubmed: 26979081
Cell. 2014 Jul 3;158(1):157-70
pubmed: 24976009
Cancer Res. 2019 Aug 15;79(16):4057-4071
pubmed: 31292163
EMBO J. 2012 Mar 7;31(5):1109-22
pubmed: 22234184
Exp Cell Res. 2013 Aug 15;319(14):2230-43
pubmed: 23791939
Acta Neuropathol. 2012 Jul;124(1):83-97
pubmed: 22249620
Tumour Biol. 2016 Oct 7;:
pubmed: 27718125
Neurosurgery. 2008 Dec;63(6):1022-33; discussion 1033-4
pubmed: 19057315
Cancer Cell. 2011 Oct 18;20(4):427-42
pubmed: 22014570
Biosci Rep. 2020 Jan 31;40(1):
pubmed: 31934721
Nat Commun. 2015 Nov 25;6:8904
pubmed: 26603103
Cancers (Basel). 2016 Jun 27;8(7):
pubmed: 27355964
Clin Cancer Res. 2008 Dec 15;14(24):8205-12
pubmed: 19088037
Biomed Res Int. 2019 Feb 20;2019:2686340
pubmed: 30915350
Cancer Cell. 2015 Dec 14;28(6):730-742
pubmed: 26669487
Stem Cells. 2009 Apr;27(4):980-7
pubmed: 19353526
Cancer Res. 2003 Sep 15;63(18):5821-8
pubmed: 14522905
Oncol Rep. 2018 Sep;40(3):1261-1274
pubmed: 30015909
Exp Cell Res. 2016 Jan 1;340(1):53-61
pubmed: 26712519
Mol Cell Ther. 2014 Sep 11;2:28
pubmed: 26056595
Oncogene. 2019 Apr;38(15):2788-2799
pubmed: 30542117
Science. 2011 Apr 22;332(6028):458-61
pubmed: 21512031
J Neuropathol Exp Neurol. 2015 Sep;74(9):889-900
pubmed: 26222502
Commun Biol. 2020 Apr 24;3(1):196
pubmed: 32332858
PLoS One. 2017 Sep 6;12(9):e0184068
pubmed: 28877210
J Biol Chem. 2016 Jul 15;291(29):15256-66
pubmed: 27231341
Breast Cancer Res. 2009;11(6):R79
pubmed: 19891787
Curr Pharm Des. 2013;19(4):634-64
pubmed: 23016862
EMBO Mol Med. 2014 May 01;6(5):651-61
pubmed: 24737870
Oncol Lett. 2018 Dec;16(6):6895-6902
pubmed: 30546421
Cancer Res. 2012 Jun 1;72(11):2822-32
pubmed: 22440753
Cell Rep. 2015 Oct 20;13(3):524-532
pubmed: 26456820
Mutat Res. 2019 Oct;846:503084
pubmed: 31585633
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8644-9
pubmed: 23650391
BMC Cancer. 2019 Jun 25;19(1):628
pubmed: 31238897
J Med Chem. 2020 Jul 9;63(13):6834-6846
pubmed: 32511917
Chemother Res Pract. 2012;2012:192362
pubmed: 22400111
Curr Pharm Des. 2014;20(41):6472-88
pubmed: 24975604
Dev Cell. 2010 Apr 20;18(4):579-91
pubmed: 20412773
Nat Commun. 2017 Dec 20;8(1):2214
pubmed: 29263426
Cancer Cell. 2006 Mar;9(3):157-73
pubmed: 16530701
Cancer Res. 2013 May 15;73(10):3132-44
pubmed: 23539443
J Neurol Sci. 2016 Aug 15;367:101-6
pubmed: 27423571
Neuro Oncol. 2010 Dec;12(12):1220-30
pubmed: 20843775
Oncotarget. 2016 Dec 27;7(52):85987-85999
pubmed: 27852064
Glia. 2002 Sep;39(3):193-206
pubmed: 12203386
Annu Rev Biochem. 2019 Jun 20;88:577-604
pubmed: 30566373
Acta Neurol Scand. 2010 Sep;122(3):159-67
pubmed: 20298491
Nat Commun. 2019 Sep 25;10(1):4363
pubmed: 31554794
Genes Dis. 2016 Mar;3(1):41-47
pubmed: 27081668
Nat Rev Drug Discov. 2012 Dec;11(12):923-36
pubmed: 23197039
Mol Cancer. 2015 Aug 21;14:160
pubmed: 26292663
J Cell Sci. 2002 Nov 1;115(Pt 21):3977-8
pubmed: 12356903
Genes Dev. 2015 Jun 15;29(12):1203-17
pubmed: 26109046
Endocr Relat Cancer. 2015 Apr;22(2):131-44
pubmed: 25560400