The SKBR3 cell-membrane proteome reveals telltales of aberrant cancer cell proliferation and targets for precision medicine applications.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 06 2022
27 06 2022
Historique:
received:
17
12
2021
accepted:
07
06
2022
entrez:
27
6
2022
pubmed:
28
6
2022
medline:
30
6
2022
Statut:
epublish
Résumé
The 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 ~ 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.
Identifiants
pubmed: 35760832
doi: 10.1038/s41598-022-14418-0
pii: 10.1038/s41598-022-14418-0
pmc: PMC9237123
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
10847Subventions
Organisme : NIGMS NIH HHS
ID : GM121920
Pays : United States
Informations de copyright
© 2022. The Author(s).
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