BAP1 suppresses prostate cancer progression by deubiquitinating and stabilizing PTEN |
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| Authors: | Rong Deng Yanmin Guo Lian Li Jianfeng He Zhe Qiang Hailong Zhang Ran Chen Yanli Wang Xian Zhao Jianxiu Yu |
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| Affiliation: | 1. Department of Biochemistry and Molecular Cell Biology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai China ; 2. Basic Clinical Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai China |
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| Abstract: | Deubiquitinase BAP1 is an important tumor suppressor in several malignancies, but its functions and critical substrates in prostate cancer (PCa) remain unclear. Here, we report that the mRNA and protein expression levels of BAP1 are downregulated in clinical PCa specimens. BAP1 can physically bind to and deubiquitinate PTEN, which inhibits the ubiquitination‐mediated degradation of PTEN and thus stabilizes PTEN protein. Ectopically expressed BAP1 in PCa cells increases PTEN protein level and subsequently inhibits the AKT signaling pathway, thus suppressing PCa progression. Conversely, knockdown of BAP1 in PCa cells leads to the decrease in PTEN protein level and the activation of the Akt signaling pathway, therefore promoting malignant transformation and cancer metastasis. However, these can be reversed by the re‐expression of PTEN. More importantly, we found that BAP1 protein level positively correlates with PTEN in a substantial fraction of human cancers. These findings demonstrate that BAP1 is an important deubiquitinase of PTEN for its stability and the BAP1‐PTEN signaling axis plays a crucial role in tumor suppression.Abbreviations- BAP1
- the BRCA1‐associated protein 1
- DUBs
- deubiquitinases
- GEO
- Gene Expression Omnibus
- IP
- immunoprecipitation
- KEGG
- the Kyoto Encyclopedia of Genes and Genomes
- PCa
- prostate cancer
- PTEN
- phosphatase and tensin homolog deleted on chromosome 10
- qRT–PCR
- quantitative real‐time polymerase chain reaction
- TCGA
- the Cancer Genome Atlas
- USP
- the ubiquitin–proteasome system
- VM
- vasculogenic mimicry
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| Keywords: | BAP1 cancer progression deubiquitination prostate cancer PTEN |
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