We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Upregulation of DR5 and Downregulation of Survivin by IITZ-01, Lysosomotropic Autophagy Inhibitor, Potentiates TRAIL-Mediated Apoptosis in Renal Cancer Cells via Ubiquitin-Proteasome Pathway.
- Authors
Shahriyar, Sk Abrar; Seo, Seung Un; Min, Kyoung-jin; Kubatka, Peter; Min, Do Sik; Chang, Jong-Soo; Kim, Dong Eun; Woo, Seon Min; Kwon, Taeg Kyu
- Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively is able to increase apoptosis in cancer cells as agent with minimum toxicity to noncancerous cells. However, all cancer cells are not sensitive to TRAIL-induced apoptosis. In this study, we showed the sub-lethal concentrations of a lysosomotropic autophagy inhibitor, IITZ-01, sensitizes cancer cells (renal, lung, and breast carcinoma) to TRAIL-induced apoptosis through DR5 upregulation and survivin downregulation through ubiquitin-proteasome pathway. Knockdown of DR5 or overexpression of survivin inhibited combined treatment with IITZ-01 and TRAIL-induced apoptosis. IITZ-01 downregulated protein expression of Cbl, ubiquitin E3 ligase, and decreased expression level of Cbl markedly led to increase DR5 protein expression and TRAIL sensitivity. Moreover, IITZ-01 decreased expression level of survivin protein via downregulation of deubiquitinase ubiquitin-specific protease 9X (USP9X) expression. Taken together, these results provide the first evidence that IITZ-01 enhances TRAIL-mediated apoptosis through DR5 stabilization by downregulation of Cbl and USP9X-dependent survivin ubiquitination and degradation in renal carcinoma cells.
- Subjects
PROTEIN metabolism; AUTOPHAGY; APOPTOSIS; CELL lines; GENE expression; KIDNEY tumors; LIGANDS (Biochemistry); LYSOSOMES; PROTEOLYTIC enzymes; SURVIVAL; TUMOR necrosis factors; CELL cycle proteins
- Publication
Cancers, 2020, Vol 12, Issue 9, p2363
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers12092363