期刊
MOLECULAR ONCOLOGY
卷 15, 期 1, 页码 279-298出版社
WILEY
DOI: 10.1002/1878-0261.12844
关键词
BAP1; cancer progression; deubiquitination; prostate cancer; PTEN
类别
资金
- NSFC (National Natural Science Foundation of China) [81630075, 81702532, 31671345, 81972585]
- China's National Key RD Programme [2019YFE0110600]
The deubiquitinase BAP1 plays a critical role in stabilizing PTEN protein levels by inhibiting its degradation, thereby suppressing the AKT signaling pathway and inhibiting tumor progression in prostate cancer. Conversely, knockdown of BAP1 leads to the decrease in PTEN protein levels and activates the Akt signaling pathway, promoting malignant transformation and cancer metastasis. The positive correlation between BAP1 and PTEN levels in human cancers highlights the importance of the BAP1-PTEN signaling axis in tumor suppression.
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.
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