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dc.contributor.authorUysal-Onganer, Pinar
dc.contributor.authorMacLatchy, Amy
dc.contributor.authorMahmoud, Rayan
dc.contributor.authorKraev, Igor
dc.contributor.authorThompson, Paul R
dc.contributor.authorInal, Jameel M.
dc.contributor.authorLange, Sigrun
dc.date2022-08-11T08:09:55.000
dc.date.accessioned2022-08-23T16:49:00Z
dc.date.available2022-08-23T16:49:00Z
dc.date.issued2020-02-22
dc.date.submitted2020-03-11
dc.identifier.citation<p>Uysal-Onganer P, MacLatchy A, Mahmoud R, Kraev I, Thompson PR, Inal JM, Lange S. Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines. Int J Mol Sci. 2020 Feb 22;21(4):1495. doi: 10.3390/ijms21041495. PMID: 32098295. <a href="https://doi.org/10.3390/ijms21041495">Link to article on publisher's site</a></p>
dc.identifier.issn1422-0067 (Linking)
dc.identifier.doi10.3390/ijms21041495
dc.identifier.pmid32098295
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41377
dc.description.abstractGlioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32098295&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHIF-1
dc.subjectStromal interaction molecule 1 (STIM-1)
dc.subjectextracellular vesicles (EVs)
dc.subjectglioblastoma multiforme (GBM)
dc.subjectmicroRNA (miR21
dc.subjectmiR126
dc.subjectmiR210)
dc.subjectmoesin
dc.subjectpeptidylarginine deiminases (PADs)
dc.subjectprohibitin (PHB)
dc.subjectprotein deimination
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectEnzymes and Coenzymes
dc.subjectMolecular Biology
dc.subjectNeoplasms
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.titlePeptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines
dc.typeJournal Article
dc.source.journaltitleInternational journal of molecular sciences
dc.source.volume21
dc.source.issue4
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5178&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4159
dc.identifier.contextkey16770737
refterms.dateFOA2022-08-23T16:49:00Z
html.description.abstract<p>Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment.</p>
dc.identifier.submissionpathoapubs/4159
dc.contributor.departmentThompson Lab
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages1495


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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).