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

Temel, Sehime Gulsun and Giray, Aslı and Karakaş, Bahriye and Gul, Ozgur and Kozanoglu, Ilknur and Celik, Husnu and Başağa, Hüveyda and Acikbas, Ufuk and Sucularli, Ceren and Oztop, Sidika and Aka, Yeliz and Kutuk, Ozgur (2020) RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells. Apoptosis, 25 (11-12). pp. 799-816. ISSN 1360-8185 (Print) 1573-675X (Online)

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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.
Item Type: Article
Uncontrolled Keywords: Bcl-2 proteins; Chemotherapy; Ovarian cancer; RAB25
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Hüveyda Başağa
Date Deposited: 03 Aug 2023 16:11
Last Modified: 03 Aug 2023 16:11
URI: https://research.sabanciuniv.edu/id/eprint/46856

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