Upregulation of Cathepsin X in Glioblastoma: Interplay with γ-Enolase and the Effects of Selective Cathepsin X Inhibitors.
cathepsin X
cathepsin X inhibitors
glioblastoma
glioblastoma stem cells
tumor microenvironment
γ-enolase
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
04 Feb 2022
04 Feb 2022
Historique:
received:
07
01
2022
revised:
28
01
2022
accepted:
01
02
2022
entrez:
15
2
2022
pubmed:
16
2
2022
medline:
17
3
2022
Statut:
epublish
Résumé
Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patient-derived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and
Identifiants
pubmed: 35163706
pii: ijms23031784
doi: 10.3390/ijms23031784
pmc: PMC8836869
pii:
doi:
Substances chimiques
CTSZ protein, human
EC 3.4.18.1
Cathepsin Z
EC 3.4.18.1
ENO2 protein, human
EC 4.2.1.11
Phosphopyruvate Hydratase
EC 4.2.1.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Slovenian Research Agency
ID : P1-0245, P1-0207, P4-0127, P1-0208, J3-2526, Z3-1870
Organisme : European Program of Cross-Border Cooperation Interreg Slovenia-Italy
ID : TRANSGLIOMA
Références
Nature. 2012 Aug 23;488(7412):522-6
pubmed: 22854781
Radiol Oncol. 2012 Sep;46(3):207-12
pubmed: 23077459
Nat Cell Biol. 2015 Feb;17(2):170-82
pubmed: 25580734
Lancet. 1981 Apr 11;1(8224):808-11
pubmed: 6111674
Biochim Biophys Acta Proteins Proteom. 2021 Feb;1869(2):140567
pubmed: 33227497
Int J Mol Sci. 2020 Jun 12;21(12):
pubmed: 32545571
Mol Carcinog. 2012 Apr;51(4):352-61
pubmed: 21538579
Genes Dev. 2014 Oct 1;28(19):2134-50
pubmed: 25274726
Cell Mol Life Sci. 2009 Mar;66(6):1126-34
pubmed: 19194656
Biochem Biophys Res Commun. 1994 Jul 15;202(1):25-30
pubmed: 8037719
Biochim Biophys Acta. 2012 Jan;1824(1):68-88
pubmed: 22024571
J Neurosurg. 1979 Mar;50(3):305-11
pubmed: 422981
Cancer Cell. 2010 Jan 19;17(1):98-110
pubmed: 20129251
J Histochem Cytochem. 2021 Dec;69(12):775-794
pubmed: 34310223
Aging Cell. 2013 Aug;12(4):604-14
pubmed: 23621429
Cancer Cell. 2021 Apr 12;39(4):509-528.e20
pubmed: 33577785
Nat Rev Drug Discov. 2006 Sep;5(9):785-99
pubmed: 16955069
Brain Sci. 2018 Feb 18;8(2):
pubmed: 29463007
Neurosci Res. 1995 Jan;21(3):191-8
pubmed: 7753500
Radiol Oncol. 2015 Aug 21;49(3):217-26
pubmed: 26401126
Semin Cancer Biol. 2015 Apr;31:76-83
pubmed: 24835450
Acta Neuropathol. 2014 Sep;128(3):347-62
pubmed: 24722970
BMC Bioinformatics. 2017 May 25;18(1):276
pubmed: 28545393
J Mol Biol. 2004 Aug 20;341(4):1015-21
pubmed: 15289101
J Neurooncol. 2002 May;58(1):21-32
pubmed: 12160137
Int J Biochem Cell Biol. 2009 Aug-Sep;41(8-9):1685-96
pubmed: 19433310
Nat Rev Neurosci. 2014 Jul;15(7):455-65
pubmed: 24946761
Biotechnol J. 2017 Oct;12(10):
pubmed: 28786556
Nat Rev Neurol. 2018 Aug;14(8):482-495
pubmed: 29985475
Cell Rep. 2017 Oct 31;21(5):1399-1410
pubmed: 29091775
Biochim Biophys Acta Mol Cell Res. 2020 Oct;1867(10):118782
pubmed: 32554164
Chem Biol. 2007 May;14(5):499-511
pubmed: 17524981
Cells. 2021 Feb 05;10(2):
pubmed: 33562819
Nat Rev Cancer. 2015 Dec;15(12):712-29
pubmed: 26597527
Cancer Cell. 2017 Mar 13;31(3):326-341
pubmed: 28292436
Oncogene. 2017 Jan 26;36(4):570-584
pubmed: 27345406
Prostate. 2004 Jul 1;60(2):109-19
pubmed: 15162377
Neurobiol Aging. 2007 Oct;28(10):1507-21
pubmed: 16959379
Oncotarget. 2017 Jul 17;8(35):59136-59147
pubmed: 28938624
Semin Cancer Biol. 2020 Feb;60:262-273
pubmed: 31654711
Biochem J. 2012 Apr 15;443(2):439-50
pubmed: 22257123
J Neurochem. 1991 Oct;57(4):1178-84
pubmed: 1895102
Neuro Oncol. 2020 Aug 17;22(8):1073-1113
pubmed: 32328653
Oncogene. 2010 Mar 18;29(11):1611-21
pubmed: 20023699
Front Mol Neurosci. 2020 Nov 20;13:575453
pubmed: 33328882
Int J Mol Sci. 2019 Jul 23;20(14):
pubmed: 31340550
Trends Pharmacol Sci. 2017 Oct;38(10):873-898
pubmed: 28668224
PLoS One. 2013;8(1):e53918
pubmed: 23326535
Nat Rev Cancer. 2007 Oct;7(10):800-8
pubmed: 17851543
J Mol Histol. 2018 Oct;49(5):481-497
pubmed: 30046941
Nucleic Acids Res. 2021 Jul 2;49(W1):W431-W437
pubmed: 33956157
Biochimie. 2008 Feb;90(2):194-207
pubmed: 17825974
Neuropharmacology. 2014 Jul;82:121-31
pubmed: 23958447
Neuro Oncol. 2021 Aug 2;23(8):1231-1251
pubmed: 34185076
Neurosignals. 2010;18(4):246-58
pubmed: 21358174
J Clin Invest. 2017 Feb 1;127(2):415-426
pubmed: 28145904
J Pathol. 2005 Sep;207(1):32-42
pubmed: 16025436
Expert Opin Biol Ther. 2006 Mar;6(3):257-79
pubmed: 16503735
JAMA. 2017 Dec 19;318(23):2306-2316
pubmed: 29260225
Oncotarget. 2017 Apr 11;8(15):25482-25499
pubmed: 28424417
Cancer Res. 2004 Oct 1;64(19):7011-21
pubmed: 15466194
BMC Cancer. 2011 Dec 20;11:524
pubmed: 22185371
Mol Neurobiol. 2014 Apr;49(2):1017-30
pubmed: 24234234
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Sci Rep. 2017 Sep 13;7(1):11459
pubmed: 28904354
Cancer Res. 2017 May 1;77(9):2266-2278
pubmed: 28235764
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Neuro Oncol. 2017 Jun 1;19(6):820-832
pubmed: 28062830
Exp Cell Res. 2005 May 15;306(1):103-13
pubmed: 15878337
Genes Dev. 2015 Jun 15;29(12):1203-17
pubmed: 26109046
Exp Neurol. 2007 Apr;204(2):525-40
pubmed: 17306794