Song Yanan, Ma Xiaokun, Zhang Miao, Wang Menghan, Wang Guoyu, Ye Ying, Xia Wei
Central Laboratory, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Nuclear Medicine, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Cell Dev Biol. 2020 Nov 10;8:588801. doi: 10.3389/fcell.2020.588801. eCollection 2020.
Ezrin, as encoded by the EZR gene, is a member of the Ezrin/Radixin/Moesin (ERM) family. The ERM family includes three highly related actin filament binding proteins, Ezrin, Radixin, and Moesin. These three members share similar structural properties containing an N-terminal domain named FERM, a central helical linker region, and a C-terminal domain that mediates the interaction with F-actin. Ezrin protein is highly regulated through the conformational change between a closed, inactivate form and an open, active form. As a membrane-cytoskeleton linker protein, Ezrin facilitates numerous signal transductions in tumorigenesis and mediates diverse essential functions through interactions with a variety of growth factor receptors and adhesion molecules. Emerging evidence has demonstrated that Ezrin is an oncogene protein, as high levels of Ezrin are associated with metastatic behavior in various types of cancer. The diverse functions attributed to Ezrin and the understanding of how Ezrin drives the deadly process of metastasis are complex and often controversial. Here by reviewing recent findings across a wide spectrum of cancer types we will highlight the structures, protein interactions and oncogenic roles of Ezrin as well as the emerging therapeutic agents targeting Ezrin. This review provides a comprehensive framework to guide future studies of Ezrin and other ERM proteins in basic and clinical studies.
由EZR基因编码的埃兹蛋白是埃兹蛋白/根蛋白/膜突蛋白（ERM）家族的成员。ERM家族包括三种高度相关的肌动蛋白丝结合蛋白，即埃兹蛋白、根蛋白和膜突蛋白。这三个成员具有相似的结构特性，包含一个名为FERM的N端结构域、一个中央螺旋连接区以及一个介导与F-肌动蛋白相互作用的C端结构域。埃兹蛋白通过在封闭的失活形式和开放的活性形式之间的构象变化受到高度调节。作为一种膜-细胞骨架连接蛋白，埃兹蛋白在肿瘤发生过程中促进众多信号转导，并通过与多种生长因子受体和黏附分子相互作用介导多种重要功能。新出现的证据表明，埃兹蛋白是一种癌基因蛋白，因为在各种类型的癌症中，高水平的埃兹蛋白与转移行为相关。归因于埃兹蛋白的多种功能以及对埃兹蛋白如何驱动致命转移过程的理解是复杂的，且常常存在争议。在这里，通过回顾各种癌症类型的最新研究发现，我们将重点介绍埃兹蛋白的结构、蛋白质相互作用和致癌作用，以及针对埃兹蛋白的新兴治疗药物。本综述提供了一个全面的框架，以指导未来在基础和临床研究中对埃兹蛋白和其他ERM蛋白的研究。
