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BAP1 suppresses prostate cancer progression by deubiquitinating and stabilizing PTEN
Rong Deng1, Yanmin Guo1, Lian Li1
1Department 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.
Molecular Oncology
|November 6, 2020
Summary
The deubiquitinase BAP1 stabilizes PTEN protein, suppressing prostate cancer (PCa) progression. Loss of BAP1 promotes PCa malignancy and metastasis by activating the AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The deubiquitinase BAP1 is a known tumor suppressor, but its role in prostate cancer (PCa) is not fully understood.
- Identifying BAP1's substrates is crucial for understanding its tumor-suppressive functions in PCa.
Purpose of the Study:
- To investigate the function of BAP1 in prostate cancer.
- To identify critical substrates of BAP1 in PCa and elucidate the underlying molecular mechanisms.
Main Methods:
- Analysis of BAP1 and PTEN expression in clinical PCa specimens.
- Co-immunoprecipitation to assess BAP1-PTEN interaction.
- In vitro studies involving ectopic expression and knockdown of BAP1 in PCa cells.
- Western blotting to evaluate protein levels and AKT signaling pathway activation.
Main Results:
- BAP1 expression is downregulated in clinical PCa.
- BAP1 directly binds and deubiquitinates PTEN, inhibiting its degradation and stabilizing PTEN protein levels.
- BAP1 suppresses PCa progression by inhibiting the AKT pathway via PTEN stabilization; conversely, BAP1 loss activates AKT signaling, promoting metastasis.
- BAP1 protein levels positively correlate with PTEN in various human cancers.
Conclusions:
- BAP1 acts as a critical deubiquitinase for PTEN, stabilizing its protein level.
- The BAP1-PTEN signaling axis is a key tumor suppressor mechanism in prostate cancer and other malignancies.
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