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dc.contributor.authorMartinez, Ramon
dc.contributor.authorHuang, Weiliang
dc.contributor.authorBuck, Heather
dc.contributor.authorRea, Samantha
dc.contributor.authorDefnet, Amy E
dc.contributor.authorKane, Maureen A
dc.contributor.authorShapiro, Paul
dc.date.accessioned2022-02-10T20:02:17Z
dc.date.available2022-02-10T20:02:17Z
dc.date.issued2022-01-18
dc.identifier.urihttp://hdl.handle.net/10713/17942
dc.description.abstractExtracellular signal-regulated kinase-1/2 (ERK1/2) pathway inhibitors are important therapies for treating many cancers. However, acquired resistance to most protein kinase inhibitors limits their ability to provide durable responses. Approximately 50% of malignant melanomas contain activating mutations in BRAF, which promotes cancer cell survival through the direct phosphorylation of the mitogen-activated protein kinase MAPK/ERK 1/2 (MEK1/2) and the activation of ERK1/2. Although the combination treatment with BRAF and MEK1/2 inhibitors is a recommended approach to treat melanoma, the development of drug resistance remains a barrier to achieving long-term patient benefits. Few studies have compared the global proteomic changes in BRAF/MEK1/2 inhibitor-resistant melanoma cells under different growth conditions. The current study uses high-resolution label-free mass spectrometry to compare relative protein changes in BRAF/MEK1/2 inhibitor-resistant A375 melanoma cells grown as monolayers or spheroids. While approximately 66% of proteins identified were common in the monolayer and spheroid cultures, only 6.2 or 3.6% of proteins that significantly increased or decreased, respectively, were common between the drug-resistant monolayer and spheroid cells. Drug-resistant monolayers showed upregulation of ERK-independent signaling pathways, whereas drug-resistant spheroids showed primarily elevated catabolic metabolism to support oxidative phosphorylation. These studies highlight the similarities and differences between monolayer and spheroid cell models in identifying actionable targets to overcome drug resistance.en_US
dc.description.urihttps://doi.org/10.1021/acsomega.1c05361en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811929/en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofACS Omegaen_US
dc.rights© 2022 The Authors. Published by American Chemical Society.en_US
dc.titleProteomic Changes in the Monolayer and Spheroid Melanoma Cell Models of Acquired Resistance to BRAF and MEK1/2 Inhibitors.en_US
dc.typeArticleen_US
dc.identifier.doi10.1021/acsomega.1c05361
dc.identifier.pmid35128241
dc.source.journaltitleACS omega
dc.source.volume7
dc.source.issue4
dc.source.beginpage3293
dc.source.endpage3311
dc.source.countryUnited States


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