계명대학교 의학도서관 Repository

Cathepsin D as a potential therapeutic target to enhance anticancer drug-induced apoptosis via RNF183-mediated destabilization of Bcl-xL in cancer cells

Metadata Downloads
Author(s)
Seung Un SeoSeon Min WooSeung-Soon ImYounghoon JangEugene HanSang Hyun KimHongchan LeeHyun-Shik LeeJu-Ock NamEdward GabrielsonKyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Im, Seung SoonHan, Eu GeneKwon, Taeg Kyu
Department
Dept. of Physiology (생리학)
Dept. of Internal Medicine (내과학)
Dept. of Immunology (면역학)
Journal Title
Cell Death Dis
Issued Date
2022
Volume
13
Abstract
Cathepsin D (Cat D) is well known for its roles in metastasis, angiogenesis, proliferation, and carcinogenesis in cancer. Despite Cat D being a promising target in cancer cells, effects and underlying mechanism of its inhibition remain unclear. Here, we investigated the plausibility of using Cat D inhibition as an adjuvant or sensitizer for enhancing anticancer drug-induced apoptosis. Inhibition of Cat D markedly enhanced anticancer drug-induced apoptosis in human carcinoma cell lines and xenograft models. The inhibition destabilized Bcl-xL through upregulation of the expression of RNF183, an E3 ligase of Bcl-xL, via NF-κB activation. Furthermore, Cat D inhibition increased the proteasome activity, which is another important factor in the degradation of proteins. Cat D inhibition resulted in p62-dependent activation of Nrf2, which increased the expression of proteasome subunits (PSMA5 and PSMB5), and thereby, the proteasome activity. Overall, Cat D inhibition sensitized cancer cells to anticancer drugs through the destabilization of Bcl-xL. Furthermore, human renal clear carcinoma (RCC) tissues revealed a positive correlation between Cat D and Bcl-xL expression, whereas RNF183 and Bcl-xL expression indicated inverse correlation. Our results suggest that inhibition of Cat D is promising as an adjuvant or sensitizer for enhancing anticancer drug-induced apoptosis in cancer cells.
Keimyung Author(s)(Kor)
임승순
한유진
권택규
Publisher
School of Medicine (의과대학)
Citation
Seung Un Seo et al. (2022). Cathepsin D as a potential therapeutic target to enhance anticancer drug-induced apoptosis via RNF183-mediated destabilization of Bcl-xL in cancer cells. Cell Death Dis, 13, 115. doi: 10.1038/s41419-022-04581-7
Type
Article
ISSN
2041-4889
Source
https://www.nature.com/articles/s41419-022-04581-7
DOI
10.1038/s41419-022-04581-7
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44177
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
공개 및 라이선스
  • 공개 구분공개
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.