BAP1 functions as a tumor promoter in prostate cancer cells through EMT regulation

Abstract

BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that has long been considered to be a tumor suppressor in various tumors, including renal cell carcinoma, uveal melanoma, mesothelioma, and cutaneous melanoma. However, the involvement of BAP1 in the progression of prostate cancer has not been studied until recently. Herein, we investigated the tumor promoting function of BAP1 in the context of prostate cancer. Analysis of The Cancer Genome Atlas (TCGA) data set showed that prostate cancer patients express high levels of BAP1 mRNA. High BAP1 expression is inversely correlated with disease-free survival in patients with prostate cancer. Among the prostate cell lines tested, BAP1 expression was high in tumorigenic and metastatic cell lines, but was low in normal prostate cell line. Knockdown of BAP1 in PC3 or DU145 cells induced mesenchymal-to-epithelial transition (MET). Further, BAP1-knockdown resulted in decreased migration and invasion of PC3 and DU145 cells. Conversely, overexpression of BAP1 in RWPE1, a normal prostate cell line, induced the migratory and invasive properties. Collectively, our findings identified that BAP1 has a tumor promoting function in prostate cancer cells, and suggest that BAP1 can serve as a potential therapeutic target for prostate cancer.

Poorly Cohesive Gastric Cancers Showing the Transcriptomic Hallmarks of Epithelial-Mesenchymal Transition Behave Aggressively

“…Reduced expression of BAP1 was previously reported to be associated to more advanced tumor stage and poor prognosis in gastric adenocarcinoma 28. Moreover, a BAP1 -mediated regulation of EMT through its deubiquitinating activity has recently been reported in prostate cancer 29. Our study is the first report suggesting the association between BAP1 mutations and the acquisition of EMT in the more aggressive among PC cancers.…”

“…28 Moreover, a BAP1-mediated regulation of EMT through its deubiquitinating activity has recently been reported in prostate cancer. 29 Our study is the first report suggesting the association between BAP1 mutations and the acquisition of EMT in the more aggressive among PC cancers. Another interesting finding is the association between the cluster A and PI3K signaling induced by FGFR family genes.…”

High expression of NPM1 via the Wnt/β‐catenin signalling pathway might predict poor prognosis for patients with prostate adenocarcinoma

“…To further explore the role of NPM1 protein in prostate cancer, NPM1 overexpression and knockdown constructs were generated and transfected into PC3 cells, and the results showed that NPM1 was positively correlated with the migration, invasion, colony‐forming and proliferation abilities of PC3 cells. The Wnt/β‐catenin signalling pathway is an important pathway in the regulation of the epithelial–mesenchymal transition (EMT), 38 and the occurrence of prostate cancer is closely related to the EMT 39 . Therefore, we hypothesised that NPM1 is related to the Wnt/β‐catenin signalling pathway in the regulation of tumour progression.…”

Targeting the Hippo Pathway in Prostate Cancer: What’s New?

“…Interestingly, the deubiquitinase BAP1 has been shown to enhance the protein stability of LATS. Somatic mutations in BAP1 are rare in PC, similar to breast, gastric and colorectal cancers [38]; however, cellular localisation may be important, with nuclear BAP1 being associated with tumour aggressiveness in a subset of patients [39][40][41]. Contrary to this, Deng et al recently published some similar experimentations with the opposite outcomes and demonstrated that BAP1 knockdown promotes tumourigenesis by stabilising PTEN [42].…”