Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells

• Published in: Cell cycle (Georgetown, Tex.) Vol. 16; no. 16; pp. 1509 - 1514
• Main Authors: Wen, Wu, Li, Jingying, Wang, Longwang, Xing, Yifei, Li, Xuechao, Ruan, Hailong, Xi, Xiaoqing, Xiong, Jianhua, Kuang, Renrui
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 18.08.2017
• Subjects: Apoptosis - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Down-Regulation - genetics; Gene Expression Regulation, Neoplastic; Humans; Nedd4 Ubiquitin Protein Ligases - antagonists & inhibitors; Nedd4 Ubiquitin Protein Ligases - metabolism; Neoplasm Invasiveness; PTEN Phosphohydrolase - metabolism; Receptors, Notch - metabolism; RNA, Small Interfering - metabolism; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; cell growth; apoptosis; invasion; NEDD4; bladder cancer
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2017.1338220

The neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) plays a pivotal oncogenic role in various types of human cancers. However, the function of NEDD4 in bladder cancer has not been fully investigated. In the present study, we aim to explore whether NEDD4 governs cell proliferation, apoptosis, migration, and invasion in bladder cancer cells. Our results showed that downregulation of NEDD4 suppressed cell proliferation in bladder cancer cells. Moreover, we found that inhibition of NEDD4 significantly induced cell apoptosis. Furthermore, downregulation of NEDD4 retarded cell migration and invasion. Notably, overexpression of NEDD4 enhanced cell growth and inhibited apoptosis. Consistently, upregulation of NEDD4 promoted cell migration and invasion in bladder cancer cells. Mechanically, our Western blotting results revealed that downregulation of NEDD4 activated PTEN and inhibited Notch-1 expression, whereas upregulation of NEDD4 reduced PTEN level and increased Notch-1 level in bladder cancer cells. Our findings indicated that NEDD4 exerts its oncogenic function partly due to regulation of PTEN and Notch-1 in bladder cancer cells. These results further revealed that targeting NEDD4 could be a useful approach for the treatment of bladder cancer.