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dc.creatorVella, Veronica
dc.creatorNicolosi, Maria Luisa
dc.creatorGiuliano, Marika
dc.creatorMorrione, Andrea
dc.creatorMalaguarnera, Roberta
dc.creatorBelfiore, Antonino
dc.date.accessioned2021-11-09T15:40:29Z
dc.date.available2021-11-09T15:40:29Z
dc.date.issued2019-09-01
dc.identifier.citationVella, V.; Nicolosi, M.L.; Giuliano, M.; Morrione, A.; Malaguarnera, R.; Belfiore, A. Insulin Receptor Isoform A Modulates Metabolic Reprogramming of Breast Cancer Cells in Response to IGF2 and Insulin Stimulation. Cells 2019, 8, 1017. https://doi.org/10.3390/cells8091017
dc.identifier.issn2073-4409
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/7057
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7077
dc.description.abstractPreviously published work has demonstrated that overexpression of the insulin receptor isoform A (IR-A) might play a role in cancer progression and metastasis. The IR has a predominant metabolic role in physiology, but the potential role of IR-A in cancer metabolic reprogramming is unknown. We aimed to characterize the metabolic impact of IR-A and its ligand insulin like growth factor 2 (IGF2) in human breast cancer (BC) cells. To establish autocrine IGF2 action, we generated human BC cells MCF7 overexpressing the human IGF2, while we focused on the metabolic effect of IR-A by stably infecting IGF1R-ablated MCF7 (MCF7IGF1R-ve) cells with a human IR-A cDNA. We then evaluated the expression of key metabolism related molecules and measured real-time extracellular acidification rates and oxygen consumption rates using the Seahorse technology. MCF7/IGF2 cells showed increased proliferation and invasion associated with aerobic glycolysis and mitochondrial biogenesis and activity. In MCF7IGF1R-ve/IR-A cells insulin and IGF2 stimulated similar metabolic changes and were equipotent in eliciting proliferative responses, while IGF2 more potently induced invasion. The combined treatment with the glycolysis inhibitor 2-deoxyglucose (2DG) and the mitochondrial inhibitor metformin blocked cell invasion and colony formation with additive effects. Overall, these results indicate that IGF2 and IR-A overexpression may contribute to BC metabolic reprogramming.
dc.format.extent26 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartCells, Vol. 8
dc.relation.isreferencedbyMDPI
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectInsulin receptor isoform A
dc.subjectIGF2
dc.subjectIGF1R
dc.subjectMetabolic reprogramming
dc.subjectAerobic glycolysis
dc.subjectMetabolic flexibility
dc.subjectBreast cancer
dc.titleInsulin Receptor Isoform A Modulates Metabolic Reprogramming of Breast Cancer Cells in Response to IGF2 and Insulin Stimulation
dc.typeText
dc.type.genreJournal article
dc.description.departmentBiology
dc.relation.doihttps://doi.org/10.3390/cells8091017
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.creator.orcidMorrione|0000-0002-2319-7884
dc.temple.creatorMorrione, Andrea
refterms.dateFOA2021-11-09T15:40:29Z


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