Loss of BAP1 Results in Growth Inhibition and Enhances Mesenchymal-Epithelial Transition in Kidney Tumor Cells.

Loss of BAP1 Results in Growth Inhibition and Enhances Mesenchymal-Epithelial Transition in Kidney Tumor Cells. Mol Cell Proteomics. 2019 Apr 16;: Authors: Chen P, Wang H, Zhang W, Chen Y, Lv Y, Wu D, Guo M, Deng H Abstract BRCA1-associated protein 1 (BAP1) is a member of the ubiquitin C‑terminal hydrolase family of deubiquitinating enzymes and is implicated in transcriptional regulation. The BAP1 gene is mutated in about 10% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, suggesting that BAP1 is a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing WT BAP1 is unclear. Here, we assessed the expression and function of BAP1 using human ccRCC specimens and cell lines. Analysis of datasets in The Cancer Genome Atlas revealed that lower BAP1 expression is correlated with longer overall survival of ccRCC patients. We established human ccRCC cell lines with stable BAP1 knockout and performed multi-omic analysis of BAP1-mediated cellular processes. BAP1 knockout downregulated proteins associated with protein synthesis, resulting in decreased cell growth. Importantly, loss of BAP1 decreased the formation of stress fibers and membrane protrusions and induced migration and invasion defects. BAP1 knockout in ccRCC cells also downregulated the expression of transcriptional repressor protein Snail and decreased the activity of Rho family GTPases, promoting ...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research