Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles

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dc.contributor.authorHánělová, Kláracs
dc.contributor.authorRaudenská, Martinacs
dc.contributor.authorKratochvílová, Monikacs
dc.contributor.authorNavrátil, Jiřícs
dc.contributor.authorVičar, Tomášcs
dc.contributor.authorBugajová, Máriacs
dc.contributor.authorGumulec, Jaromírcs
dc.contributor.authorMasařík, Michalcs
dc.contributor.authorBalvan, Jancs
dc.coverage.issue1cs
dc.coverage.volume21cs
dc.date.accessioned2023-08-01T10:58:27Z
dc.date.available2023-08-01T10:58:27Z
dc.date.issued2023-05-24cs
dc.description.abstractExtracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGF ss 1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-a, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators.en
dc.formattextcs
dc.format.extent1-21cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationCell Communication and Signaling. 2023, vol. 21, issue 1, p. 1-21.en
dc.identifier.doi10.1186/s12964-023-01126-zcs
dc.identifier.issn1478-811Xcs
dc.identifier.orcid0000-0002-9136-7873cs
dc.identifier.orcid0000-0002-9658-3444cs
dc.identifier.other183987cs
dc.identifier.researcheridC-6006-2018cs
dc.identifier.researcheridD-7638-2012cs
dc.identifier.scopus57202426072cs
dc.identifier.scopus55769747816cs
dc.identifier.urihttp://hdl.handle.net/11012/213627
dc.language.isoencs
dc.publisherBMCcs
dc.relation.ispartofCell Communication and Signalingcs
dc.relation.urihttps://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01126-zcs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1478-811X/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectExtracellular vesiclesen
dc.subjectPhosphatidylserine-positive extracellular vesiclesen
dc.subjectAutophagyen
dc.subjectAutophagy modulationen
dc.subjectHead and neck canceren
dc.subjectProteomicsen
dc.subjectSQSTM1en
dc.subjectSenescenceen
dc.subjectp21en
dc.subjectAutophiniben
dc.subjectCPD18en
dc.subjectEACCen
dc.subjectBafilomycin A1en
dc.subject3-hydroxychloroquineen
dc.subjectRapamycinen
dc.subjectNVP-BEZ235en
dc.subjectTorin1en
dc.subjectStarvationen
dc.titleAutophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesiclesen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-183987en
sync.item.dbtypeVAVen
sync.item.insts2023.08.01 12:58:27en
sync.item.modts2023.08.01 12:20:03en
thesis.grantorVysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií. Ústav biomedicínského inženýrstvícs
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