The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells

• Published in: International journal of molecular sciences Vol. 25; no. 10; p. 5559
• Main Authors: Lin, Yi-Hsuan, Chen, Tzu-Min, Tsai, Yu-Ling, Tsai, Wen-Chiuan, Wang, Hisao-Hsien, Chen, Ying, Wu, Sheng-Tang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.05.2024
• Subjects: Angiogenesis; Animals; Bladder cancer; Breast cancer; Cancer; Cancer cells; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - genetics; Cysteine Endopeptidases; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypoxia; Lung cancer; Male; Metastasis; Mice; migration; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Nitric oxide; Oncology, Experimental; Prevention; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - metabolism; Protein expression; Proteins; PSMB4; Scientific equipment and supplies industry; tube formation; Tumor Microenvironment - genetics; Tumors; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; United States; Massachusetts; Taiwan; tube formation; migration; PSMB4; angiogenesis; bladder cancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25105559

Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.