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

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Temel, Şehime Gülsün

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Giray, Aslı
Karakaş, Bahriye
Gül, Özgür
Kozanoğlu, İlknur
Çelik, Hüsnü
Başağa, Hüveyda
Açıkbaş, Ufuk
Suçularlı, Ceren
Öztop, Sıdıka
Aka, Yeliz

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Springer

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Abstract

Ovarian 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.

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Keywords

Rab25, Chemotherapy, Bcl-2 proteins, Ovarian cancer, Bcl-2, Expression, Metasis, Inhibition, Invasion, Overexpression, Proliferation, Contributes, Biomarkers, Kidney, Biochemistry & molecular biology, Cell biology

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Temel, S. G. vd. (2020). ''RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells''. Apoptosis, 25(11-12), 799-816.

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