The SKBR3 cell-membrane proteome reveals telltales of aberrant cancer cell proliferation and targets for precision medicine applications

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dc.contributor.authorKarcini, Arbaen
dc.contributor.authorLazar, Iulia M.en
dc.date.accessioned2022-11-14T17:59:11Zen
dc.date.available2022-11-14T17:59:11Zen
dc.date.issued2022-06-27en
dc.description.abstractThe plasma membrane proteome resides at the interface between the extra- and intra-cellular environment and through its various roles in signal transduction, immune recognition, nutrient transport, and cell-cell/cell-matrix interactions plays an absolutely critical role in determining the fate of a cell. Our work was aimed at exploring the cell-membrane proteome of a HER2+ breast-cancer cell line (SKBR3) to identify triggers responsible for uncontrolled cell proliferation and intrinsic resources that enable detection and therapeutic interventions. To mimic environmental conditions that enable cancer cells to evolve adaptation/survival traits, cell culture was performed under serum-rich and serum-deprived conditions. Proteomic analysis enabled the identification of similar to 2000 cell-membrane proteins. Classification into proteins with receptor/enzymatic activity, CD antigens, transporters, and cell adhesion/junction proteins uncovered overlapping roles in processes that drive cell growth, apoptosis, differentiation, immune response, adhesion and migration, as well as alternate pathways for proliferation. The large number of tumor markers (> 50) and putative drug targets (> 100) exposed a vast potential for yet unexplored detection and targeting opportunities, whereas the presence of 15 antigen immunological markers enabled an assessment of epithelial, mesenchymal or stemness characteristics. Serum-starved cells displayed altered processes related to mitochondrial OXPHOS/ATP synthesis, protein folding and localization, while serum-treated cells exhibited attributes that support tissue invasion and metastasis. Altogether, our findings advance the understanding of the biological triggers that sustain aberrant cancer cell proliferation, survival and development of resistance to therapeutic drugs, and reveal vast innate opportunities for guiding immunological profiling and precision medicine applications aimed at target selection or drug discovery.en
dc.description.notesThis work was supported by an award from the National Institute of General Medical Sciences (Grant No. 1R01GM121920) to IML. We thank Dr. Joshua Nicklay and Dr. John Veneski from Thermo Scientific for analyzing a preliminary set of cell extracts on a QExactive Plus Orbitrap mass spectrometer. We also thank Dr. Samy Lamouille and Christina Wheeler from the Fralin Biomedical Research Institute at VTC for providing support with the acquisition of confocal microscopy data.en
dc.description.sponsorshipNational Institute of General Medical Sciences [1R01GM121920]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-022-14418-0en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.other10847en
dc.identifier.pmid35760832en
dc.identifier.urihttp://hdl.handle.net/10919/112585en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherNature Portfolioen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjecttherapeutic targetsen
dc.subjectadhesion gpcrsen
dc.subjectatp synthaseen
dc.subjectreceptoren
dc.subjectidentificationen
dc.subjectmetabolismen
dc.subjectmtoren
dc.titleThe SKBR3 cell-membrane proteome reveals telltales of aberrant cancer cell proliferation and targets for precision medicine applicationsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Biological Sciences
Scholarly Works, Fralin Life Sciences Institute
Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)