RAB25 confers resistance to chemotherapy by altering mitochondrial apoptosis signaling in ovarian cancer cells
Küçük Resim Yok
Tarih
2020
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Rab25, Chemotherapy, Bcl-2 Proteins, Ovarian Cancer, Bcl-2, Expression, Metastasis, Inhibition, Invasion, Overexpression, Proliferation, Contributes, Biomarkers, Kidney
Kaynak
Apoptosis
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
25
Sayı
11.Ara
