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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
dc.contributor.authorLange, Sigrun
dc.date.accessioned2020-03-25T01:11:43Z
dc.date.available2020-03-25T01:11:43Z
dc.date.issued2020-02-22
dc.identifier.citationUysal-Onganer , P , MacLatchy , A , Mahmoud , R , Kraev , I , Thompson , P R , Inal , J & Lange , S 2020 , ' Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines ' , International Journal of Molecular Sciences , vol. 21 , no. 4 , 1495 . https://doi.org/10.3390/ijms21041495
dc.identifier.issn1422-0067
dc.identifier.otherPURE: 19869944
dc.identifier.otherPURE UUID: b83cfbcd-cefd-41a8-a419-c637132202a1
dc.identifier.otherScopus: 85079877943
dc.identifier.urihttp://hdl.handle.net/2299/22483
dc.descriptionFunding Information: Funding: This work was supported in parts by a University of Westminster Start-up Grants to S.L. and P.U.-O. Funding Information: Acknowledgments: The authors would like to thank Yagnesh Umrania and Michael Deery at the Cambridge Centre for Proteomics for the LC-MS/MS analysis. Thanks are due to The Guy Foundation for funding the purchase of equipment utilised in this work. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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.en
dc.format.extent29
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.subjectExtracellular vesicles (EVs)
dc.subjectGlioblastoma multiforme (GBM)
dc.subjectHIF-1
dc.subjectMiR126
dc.subjectMiR210)
dc.subjectMicroRNA (miR21
dc.subjectMoesin
dc.subjectPeptidylarginine deiminases (PADs)
dc.subjectProhibitin (PHB)
dc.subjectProtein deimination
dc.subjectStromal interaction molecule 1 (STIM-1)
dc.subjectCatalysis
dc.subjectMolecular Biology
dc.subjectSpectroscopy
dc.subjectComputer Science Applications
dc.subjectPhysical and Theoretical Chemistry
dc.subjectOrganic Chemistry
dc.subjectInorganic Chemistry
dc.titlePeptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Linesen
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionExtracellular Vesicle Research Unit
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85079877943&partnerID=8YFLogxK
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.3390/ijms21041495
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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