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Cathepsin K inhibition-induced mitochondrial ROS enhances sensitivity of cancer cells to anti-cancer drugs through USP27x-mediated Bim protein stabilization

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Author(s)
Seung Un SeoSeon Min WooMin Wook KimHyun-Shik LeeSang Hyun KimSun Chul KangEun-Woo LeeKyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Redox biology.
Issued Date
2019
Volume
30
Keyword
ApoptosisBimCathepsin KMitochondriaRaptorUSP27x
Abstract
Cathepsin K (Cat K) is expressed in cancer cells, but the effect of Cat K on apoptosis is still elusive. Here, we showed that inhibition of Cat K sensitized the human carcinoma cells to anti-cancer drug through up-regulation of Bim. Inhibition of Cat K increased USP27x expression, and knock down of USP27x markedly blocked Cat K-induced up-regulation of Bim expression. Furthermore, inhibition of Cat K induced proteasome-dependent degradation of regulatory associated protein of mammalian target of rapamycin (Raptor). Down-regulation of Raptor expression increased mitochondrial ROS production, and mitochondria specific superoxide scavengers prevented USP27x-mediated stabilization of Bim by inhibition of Cat K. Moreover, combined treatment with Cat K inhibitor (odanacatib) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reduced tumor growth and induced cell death in a xenograft model. Our results demonstrate that Cat K inhibition enhances anti-cancer drug sensitivity through USP27x-mediated the up-regulation of Bim via the down-regulation of Raptor.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Seung Un Seo et al. (2019). Cathepsin K inhibition-induced mitochondrial ROS enhances sensitivity of cancer cells to anti-cancer drugs through USP27x-mediated Bim protein stabilization. Redox biology., 30, 101422–101422. doi: 10.1016/j.redox.2019.101422
Type
Article
ISSN
2213-2317
Source
https://www.sciencedirect.com/science/article/pii/S2213231719314569?via%3Dihub
DOI
10.1016/j.redox.2019.101422
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/42648
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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