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

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 f

SUBMITTER: Seo SU 

PROVIDER: S-EPMC6948260 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature