Treatment based on BRAF/MEK kinase inhibitors is currently one of the most commonly used methods in melanoma therapy. Unfortunately, in the case of advanced melanoma, patients often develop resistance to treatment at an early stage of the treatment. A thorough understanding of the causes and mechanisms may contribute to the development of new, more effective treatments. One of the ways in which treatment-resistant cells can affect other cancer cells and the tumor microenvironment is through the factors they secrete. Therefore, this study aimed to examine the protein composition of the secretome of cells resistant to vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor) and compare it with the secretome of non-resistant cells. Proteomic analysis, followed by gene ontology (GO) analysis, identified many differences in resistant melanoma cells' secretomes compared to controls (non-resistant) in terms of cellular compartment, molecular function, biological processes, and reactome pathways. Proteins unique to the secretomes of resistant cells were associated with, among others, integrin binding and interactions, and the extracellular matrix organization. Other interesting groups of proteins, i.e., up- or downregulated in secretomes of resistant melanoma cells vs their non-resistant variants, were directly related to cancer progression and associated with cell adhesion, actin cytoskeleton organization, matrix proteolysis, and drug resistance. Proteins included in these groups, once secreted by resistant melanoma cells, can undoubtedly influence the surrounding microenvironment in a way that promotes the formation of a pro-tumor niche.
[doi:10.25345/C5WH2DT5N]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: melanoma ; drug resistance ; secretome ; BRAF inhibitor ; vemurafenib ; cobimetinib ; MEK inhibitor ; DatasetType:Proteomics
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Principal Investigators: (in alphabetical order) |
Aleksandra Simiczyjew, Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, Poland |
| Submitting User: | msurman |
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