Mapping the cell-membrane proteome of the SKBR3/HER2+ cell line to the cancer hallmarks

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dc.contributor.authorLazar, Iulia M.en
dc.contributor.authorKarcini, Arbaen
dc.contributor.authorHaueis, Joshua R. S.en
dc.contributor.editorNassa, Giovannien
dc.date.accessioned2022-11-16T14:09:42Zen
dc.date.available2022-11-16T14:09:42Zen
dc.date.issued2022-08-01en
dc.date.updated2022-11-16T03:20:49Zen
dc.description.abstractThe hallmarks of biological processes that underlie the development of cancer have been long recognized, yet, existing therapeutic treatments cannot prevent cancer from continuing to be one of the leading causes of death worldwide. This work was aimed at exploring the extent to which the cell-membrane proteins are implicated in triggering cancer hallmark processes, and assessing the ability to pinpoint tumor-specific therapeutic targets through a combined membrane proteome/cancer hallmark perspective. By using GO annotations, a database of human proteins associated broadly with ten cancer hallmarks was created. Cell-membrane cellular subfractions of SKBR3/HER2+ breast cancer cells, used as a model system, were analyzed by high resolution mass spectrometry, and high-quality proteins (FDR<3%) identified by at least two unique peptides were mapped to the cancer hallmark database. Over 1,400 experimentally detected cell-membrane or cell-membrane associated proteins, representing ~18% of the human cell-membrane proteome, could be matched to the hallmark database. Representative membrane constituents such as receptors, CDs, adhesion and transport proteins were distributed over the entire genome and present in every hallmark category. Sustained proliferative signaling/cell cycle, adhesion/tissue invasion, and evasion of immune destruction emerged as prevalent hallmarks represented by the membrane proteins. Construction of protein-protein interaction networks uncovered a high level of connectivity between the hallmark members, with some receptor (EGFR, ERBB2, FGFR, MTOR, CSF1R), antigen (CD44), and adhesion (MUC1) proteins being implicated in most hallmark categories. An illustrative subset of 138 hallmark proteins that included 42 oncogenes, 24 tumor suppressors, 9 oncogene/tumor suppressor, and 45 approved drug targets was subjected to a more in-depth analysis. The existing drug targets were implicated mainly in signaling processes. Network centrality analysis revealed that nodes with high degree, rather than betweenness, represent a good resource for informing the selection of putative novel drug targets. Through heavy involvement in supporting cancer hallmark processes, we show that the functionally diverse and networked landscape of cancer cell-membrane proteins fosters unique opportunities for guiding the development of novel therapeutic interventions, including multi-agent, immuno-oncology and precision medicine applications.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0272384en
dc.identifier.eissn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue8 Augusten
dc.identifier.orcidLazar, Maria [0000-0001-7746-7889]en
dc.identifier.otherPONE-D-22-11202 (PII)en
dc.identifier.pmid35913978en
dc.identifier.urihttp://hdl.handle.net/10919/112650en
dc.identifier.volume17en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35913978en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPreventionen
dc.subjectBreast Canceren
dc.subjectCanceren
dc.subjectBiotechnologyen
dc.subject2.1 Biological and endogenous factorsen
dc.subject2 Aetiologyen
dc.subject3 Good Health and Well Beingen
dc.subject.meshCell Lineen
dc.subject.meshCell Line, Tumoren
dc.subject.meshHumansen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshReceptor, erbB-2en
dc.subject.meshMembrane Proteinsen
dc.subject.meshProteomeen
dc.subject.meshFemaleen
dc.subject.meshPrecision Medicineen
dc.titleMapping the cell-membrane proteome of the SKBR3/HER2+ cell line to the cancer hallmarksen
dc.title.serialPLoS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-07-18en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Psychiatry and Behavioral Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Psychiatry and Behavioral Medicine/Secondary Appointment-Psychiatry and Behavioral Medicineen

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