Pyruvate dehydrogenase contributes to drug resistance of lung cancer cells through epithelial mesenchymal transition

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dc.authoridEngin Ulukaya / 0000-0003-4875-5472en_US
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.contributor.authorCevatemre, B.
dc.contributor.authorUlukaya, Engin
dc.contributor.authorDere, E.
dc.contributor.authorDilege, S.
dc.contributor.authorAçılan, C.
dc.date.accessioned2022-02-02T12:52:02Z
dc.date.available2022-02-02T12:52:02Z
dc.date.issued2022en_US
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractRecently, there has been a growing interest on the role of mitochondria in metastatic cascade. Several reports have shown the preferential utilization of glycolytic pathway instead of mitochondrial respiration for energy production and the pyruvate dehydrogenase (PDH) has been considered to be a contributor to this switch in some cancers. Since epithelial mesenchymal transition (EMT) is proposed to be one of the significant mediators of metastasis, the molecular connections between cancer cell metabolism and EMT may reveal underlying mechanisms and improve our understanding on metastasis. In order to explore a potential role for PDH inhibition on EMT and associated drug resistance, we took both pharmacological and genetic approaches, and selectively inhibited or knocked down PDHA1 by using Cpi613 and shPDHA1, respectively. We found that both approaches triggered morphological changes and characteristics of EMT (increase in mesenchymal markers). This change was accompanied by enhanced wound healing and an increase in migration. Interestingly, cells were more resistant to many of the clinically used chemotherapeutics following PDH inhibition or PDHA1 knockdown. Furthermore, the TGF?RI (known as a major inducer of the EMT) inhibitor (SB-431542) together with the PDHi, was effective in reversing EMT. In conclusion, interfering with PDH induced EMT, and more importantly resulted in chemoresistance. Therefore, our study demonstrates the need for careful consideration of PDH-targeting approaches in cancer treatment. Copyright © 2022 Cevatemre, Ulukaya, Dere, Dilege and Acilan.en_US
dc.identifier.citationCevatemre, B., Ulukaya, E., Dere, E., Dilege, S., & Acilan, C. (2022). Pyruvate dehydrogenase contributes to drug resistance of lung cancer cells through epithelial mesenchymal transition. Frontiers in Cell and Developmental Biology, 9 doi:10.3389/fcell.2021.738916en_US
dc.identifier.doi10.3389/fcell.2021.738916en_US
dc.identifier.issn2296-634Xen_US
dc.identifier.scopus2-s2.0-85123438941en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3389/fcell.2021.738916
dc.identifier.urihttps://hdl.handle.net/20.500.12713/2454
dc.identifier.volume9en_US
dc.identifier.wosWOS:000757362000001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorUlukaya, Engin
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Cell and Developmental Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCancer Metabolismen_US
dc.subjectDrug Resistanceen_US
dc.subjectEpithelial Mesenchymal Transitionen_US
dc.subjectLung Canceren_US
dc.subjectPyruvate Dehydrogenase Complexen_US
dc.titlePyruvate dehydrogenase contributes to drug resistance of lung cancer cells through epithelial mesenchymal transitionen_US
dc.typeArticleen_US

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