Journal of translational medicine · 2025
Protein kinase D2-mediated maintenance complex component 2 phosphorylation promotes bladder cancer progression.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tian He, Song Jing, Cong Junzi, Zhang Zhihui, Di Yancheng, Yan Benchun, Nan Xihao
Аннотация
BACKGROUND: Bladder cancer, a widely occurring malignant tumor worldwide, is closely related to the abnormal activation of numerous signaling pathways during its initiation, progression, and metastasis. Protein kinase D2 (PRKD2), as a member of the protein kinase D family, exerts a pivotal influence on human cancers. This research aimed to elucidate the involvement and mechanism of PRKD2 in bladder cancer.
METHODS: PRKD2 expression was analyzed using quantitative real-time PCR, Western blotting and tissue microarray (n = 30). Functional experiments were conducted to evaluate the biological phenotypes of cells, including CCK-8 assay, colony formation assay, flow cytometry analysis, scratch wound healing assay, Transwell migration assay, and mouse xenograft model. The phosphorylation of MCM2 by PRKD2 was examined using site-directed mutagenesis and immunoprecipitation assay assays.
RESULTS: Our results revealed markedly elevated expression levels of PRKD2 in bladder cancer compared to control tissues. Increased PRKD2 expression was associated with lymph node metastasis, distant metastasis, advanced TNM staging, and poorer prognosis. Functional experiments demonstrated that depletion of PRKD2 impeded the proliferation, migration, invasion, and epithelial-mesenchymal transition of bladder cancer cells in vitro and in vivo. Mechanistically, PRKD2 phosphorylates complex component 2 (MCM2) at serine 139. This phosphorylation drives the malignant progression of bladder cancer cells.
CONCLUSIONS: These findings offer new insights into regulatory mechanisms involving PRKD2 contributing to the malignancy of bladder cancer, thereby presenting a potential therapeutic target.
METHODS: PRKD2 expression was analyzed using quantitative real-time PCR, Western blotting and tissue microarray (n = 30). Functional experiments were conducted to evaluate the biological phenotypes of cells, including CCK-8 assay, colony formation assay, flow cytometry analysis, scratch wound healing assay, Transwell migration assay, and mouse xenograft model. The phosphorylation of MCM2 by PRKD2 was examined using site-directed mutagenesis and immunoprecipitation assay assays.
RESULTS: Our results revealed markedly elevated expression levels of PRKD2 in bladder cancer compared to control tissues. Increased PRKD2 expression was associated with lymph node metastasis, distant metastasis, advanced TNM staging, and poorer prognosis. Functional experiments demonstrated that depletion of PRKD2 impeded the proliferation, migration, invasion, and epithelial-mesenchymal transition of bladder cancer cells in vitro and in vivo. Mechanistically, PRKD2 phosphorylates complex component 2 (MCM2) at serine 139. This phosphorylation drives the malignant progression of bladder cancer cells.
CONCLUSIONS: These findings offer new insights into regulatory mechanisms involving PRKD2 contributing to the malignancy of bladder cancer, thereby presenting a potential therapeutic target.