RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells

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dc.contributor.authorTemel, Şehime Gülsün
dc.contributor.authorGiray, Aslı
dc.contributor.authorKarakaş, Bahriye
dc.contributor.authorGül,Özgür
dc.contributor.authorKozanoğlu, İlknur
dc.contributor.authorÇelik, Hüsnü
dc.contributor.authorKütük, Özgür
dc.date.accessioned2021-02-19T21:16:17Z
dc.date.available2021-02-19T21:16:17Z
dc.date.issued2020
dc.departmentALKÜ
dc.descriptionKUTUK, OZGUR/0000-0001-9854-7220; OZTOP, SIDIKA/0000-0001-5653-6080
dc.description.abstractOvarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian cancer cells. BH3 profiling assays corroborated that RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by means of RNAi or RFP14 inhibitory hydrocarbon-stapled peptide sensitizes ovarian cancer cells to chemotherapy as well as RAB25-mediated proliferation, invasion and migration. Our data suggest that RAB25 is a potential therapeutic target for ovarian cancer.
dc.description.sponsorshipTUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113S871]; Baskent University Research FundsBaskent University; Science Academy BAGEP program
dc.description.sponsorshipThis study was supported by TUBITAK 113S871 and Baskent University Research Funds. Ozgur Kutuk acknowledges support from the Science Academy BAGEP program.
dc.identifier.doi10.1007/s10495-020-01635-z
dc.identifier.endpage816en_US
dc.identifier.issn1360-8185
dc.identifier.issn1573-675X
dc.identifier.issue11-12en_US
dc.identifier.pmid32901335
dc.identifier.scopusqualityQ1
dc.identifier.startpage799en_US
dc.identifier.urihttps://doi.org/10.1007/s10495-020-01635-z
dc.identifier.urihttps://hdl.handle.net/20.500.12868/361
dc.identifier.volume25en_US
dc.identifier.wosWOS:000567421400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthor0-belirlenecek
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofApoptosis
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectRAB25
dc.subjectChemotherapy
dc.subjectBcl-2 proteins
dc.subjectOvarian cancer
dc.titleRAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells
dc.typeArticle

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