Qiu Jing, Tang Yongping, Liu Lan, Yu Jiangbo, Chen Zhenggang, Chen Hao, Yuan Rongtao
Department of Stomatology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China.
Front Oncol. 2022 Aug 22;12:815998. doi: 10.3389/fonc.2022.815998. eCollection 2022.
The Disheveled, EGL-10, Pleckstrin domain containing 1 (DEPDC1) is a new oncogene that has recently been described. The mechanisms and functions of its expression are yet to be determined in oral squamous cell carcinoma (OSCC). In the present study, the impact of DEPDC1 on the growth and development of OSCC was investigated using animal models, cell lines and human tissue samples. Elevated DEPDC1 expression within cancer cell lines and human OSCC has been identified. Mechanistic examination showed that restored DEPDC1 expression and stimulated OSCC tumour development. In addition, FOXM1 interacts with DEPDC1 as indicated by co-immunoprecipitation and immunofluorescence testing. Functionally, DEPDC1 facilitated Wnt/β-catenin signal transduction and β-catenin protein nuclear expression. In summary, the DEPDC1, interacting with FOXM1 Wnt/β-catenin signaling, the closely regulated OSCC pathogenesis, suggesting that targeting the novel DEPDC1/FOXM1/β-catenin complex is an essential OSCC therapeutic approach.
含去卷曲蛋白、EGL-10、普列克底物蛋白结构域1(DEPDC1)是一种最近被描述的新致癌基因。其在口腔鳞状细胞癌(OSCC)中的表达机制和功能尚未确定。在本研究中,使用动物模型、细胞系和人体组织样本研究了DEPDC1对OSCC生长和发展的影响。已确定癌细胞系和人类OSCC中DEPDC1表达升高。机制研究表明,恢复DEPDC1表达会促进OSCC肿瘤发展。此外,免疫共沉淀和免疫荧光检测表明,FOXM1与DEPDC1相互作用。在功能上,DEPDC1促进Wnt/β-连环蛋白信号转导和β-连环蛋白蛋白的核表达。总之,DEPDC1与FOXM1相互作用,调控Wnt/β-连环蛋白信号传导,密切调节OSCC发病机制,这表明靶向新型DEPDC1/FOXM1/β-连环蛋白复合物是一种重要的OSCC治疗方法。