WD repeat protein 54-mediator of ErbB2-driven cell motility 1 axis promotes bladder cancer tumorigenesis and metastasis and impairs chemosensitivity. (1st March 2023)

• Record Type: Journal Article
• Authors: Wei, Xiaosong; Wang, Beibei; Wu, Zixin; Yang, Xiaoming; Guo, Yufeng; Yang, Yang; Fang, Zhiwei; Yi, Chengzhi; Zhang, Liuhui; Fan, Xin; Zhang, Lirong; Song, Dongkui
• Is Part Of: Cancer letters. Volume 556(2023)
• Publication Date: 2023-03-01
• Subjects: Bladder cancer -- WD repeat Domain 54 -- Mediator of ErbB2-driven cell motility 1 -- Protein-protein interaction; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2023.216058
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: One of the most abundant protein-protein interaction domains in the human proteome is the WD40 repeat (WDR) domain. A Gene Expression Omnibus dataset revealed 37 differentially expressed WDR domain genes in bladder cancer (BC). WD repeat domain 54 ( WDR54 ), an upregulated WDR domain gene, was selected for further investigation. Sixty pairs of frozen BC tumor and non-malignant bladder tissues and 83 paraffin-embedded BC tissue specimens were obtained. Loss-/gain-of-function experiments were carried out using BC and xenograft tumor models. WDR54 was overexpressed in BC cells, and its high expression was linked to tumor stage and lymph node metastases in patients. WDR54 contributed to the tumorigenesis and metastasis of BC and impaired its chemosensitivity. WDR54 prevented the degradation and ubiquitination of the mediator of ErbB2-driven cell motility 1 (MEMO1). WDR54 also promoted the interaction between MEMO1 and insulin receptor substrate 1 (IRS1) and activated the IRS1/AKT/β-catenin pathway in BC cells. Particularly, WDR54 depended on MEMO1 to exert its biological functions. Our study demonstrated the relevance of WDR54 in BC and provides insight into the molecular mechanism underlying BC. Highlights: WDR54 promotes bladder cancer tumorigenesis and metastasis. MEMO1 promotes bladder cancer cell proliferation and motility in vitro. WDR54 and MEMO1 reduce cisplatin sensitivity in bladder cancer cells. WDR54 increases the protein stability of MEMO1 and its interaction with IRS1. The biological functions of WDR54 dependent on MEMO1 in bladder cancer.