Insights Into the Mechanism of Anticancer Drug Imatinib Revealed Through Multi-Omic Analyses in Yeast

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dc.authoridTaymaz-Nikerel, Hilal/0000-0002-5523-263X|Eraslan, Serpil/0000-0002-7674-7384
dc.authorwosidTaymaz-Nikerel, Hilal/AAQ-9395-2021
dc.authorwosidKirdar, Betul/ABI-7250-2020
dc.contributor.authorTaymaz-Nikerel, Hilal
dc.contributor.authorEraslan, Serpil
dc.contributor.authorKirdar, Betul
dc.date.accessioned2024-07-18T20:45:36Z
dc.date.available2024-07-18T20:45:36Z
dc.date.issued2020
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractImatinib mesylate is a receptor tyrosine kinase inhibitor drug with broad applications in cancer therapeutics, for example, in chronic myeloid leukemia and gastrointestinal stromal tumors. In this study, new multi-omics findings in yeast on the mechanism of imatinib are reported, using the model organismSaccharomyces cerevisiae. Whole-genome analysis of the transcriptional response of yeast cells following long-term exposure to imatinib, flux-balance analysis (FBA), and modular analysis of protein/protein interaction network consisting of proteins encoded by differentially expressed genes (DEGs) were performed. DEGs indicated that carbon, nitrogen, starch, sucrose, glyoxylate/dicarboxylate metabolism, valine and leucine degradation, and tricarboxylic acid cycle (TCA) were significantly upregulated. By contrast, ribosome biogenesis, pentose/glucuronate interconversion, tryptophan/pyruvate metabolic pathways, and meiosis were significantly downregulated. FBA revealed that a large set of metabolic pathways was altered by imatinib to compensate cancer-associated metabolic changes. Integration of transcriptome and interactome (protein/protein interactions) data helped to identify the core regulatory genes and pathways through elucidation of the active subnetworks. It appears that imatinib may also contribute to antitumoral immune response in the tumor microenvironment and most of the metabolic rearrangements are at posttranscriptional level. Furthermore, additional support for possible contribution of thiamine/pyridoxal phosphate biosynthesis and mitogen-activated protein kinase pathway to drug resistance is noted. This report advances multi-omics understanding of the mechanism of imatinib, and by extension, offers new molecular avenues toward precision medicine and discovery of novel drug targets in cancer therapeutics.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [114C062]en_US
dc.description.sponsorshipThis research was funded by The Scientific and Technological Research Council of Turkey (TUBITAK) through Project No. 114C062.en_US
dc.identifier.doi10.1089/omi.2020.0144
dc.identifier.endpage678en_US
dc.identifier.issn1536-2310
dc.identifier.issn1557-8100
dc.identifier.issue11en_US
dc.identifier.pmid32991258en_US
dc.identifier.scopus2-s2.0-85095799606en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage667en_US
dc.identifier.urihttps://doi.org/10.1089/omi.2020.0144
dc.identifier.urihttps://hdl.handle.net/11411/7622
dc.identifier.volume24en_US
dc.identifier.wosWOS:000574628200001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMary Ann Liebert, Incen_US
dc.relation.ispartofOmics-A Journal of Integrative Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectİmatiniben_US
dc.subjectCanceren_US
dc.subjectMulti-Omicsen_US
dc.subjectYeasten_US
dc.subjectProteinen_US
dc.subjectProtein İnteractionsen_US
dc.subjectSystems Biologyen_US
dc.subjectKinase Inhibitor Imatiniben_US
dc.subjectAmino-Acid-Metabolismen_US
dc.subjectFunctional-Analysisen_US
dc.subjectInduced Apoptosisen_US
dc.subjectLeukemiaen_US
dc.subjectResistanceen_US
dc.subjectCanceren_US
dc.subjectPathwayen_US
dc.subjectActivationen_US
dc.subjectMutationsen_US
dc.titleInsights Into the Mechanism of Anticancer Drug Imatinib Revealed Through Multi-Omic Analyses in Yeasten_US
dc.typeArticleen_US

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