Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts.

Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts. Oncogenesis. 2019 Feb 22;8(3):15 Authors: Chen CH, Bhasin S, Khanna P, Joshi M, Joslin PM, Saxena R, Amin S, Liu S, Sindhu S, Walker SR, Catalano P, Frank DA, Alper SL, Bhasin M, Bhatt RS Abstract Several therapeutic options are available for metastatic RCC, but responses are almost never complete, and resistance to therapy develops in the vast majority of patients. Consequently, novel treatments are needed to combat resistance to current therapies and to improve patient outcomes. We have applied integrated transcriptome and proteome analyses to identify cathepsin B (CTSB), a cysteine proteinase of the papain family, as one of the most highly upregulated gene products in established human RCC xenograft models of resistance to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). We used established RCC models to test the significance of CTSB in the progression of renal cancer. Our evaluation of CTSB showed that stable CTSB knockdown suppressed RCC growth in vitro and in vivo. Stable over-overexpression of wild-type CTSB (CTSBwt/hi), but not of an CTSB active site mutant (CTSBN298A), rescued cell growth in CTSB knockdown cells and abolished the efficacy of VEGFR TKI treatment. Genome-wide transcriptome profiling of CTSB knockdown cells demonstrated significant effects on multiple metabolic and stem cell-related p...
Source: Genomics Proteomics ... - Category: Genetics & Stem Cells Authors: Tags: Oncogenesis Source Type: research