Xu Cong, Wang Feng, Hao Li, Liu Jing, Shan Benjie, Lv Shuhua, Han Xinghua, Pan Yueyin, Niu Yun
Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Front Oncol. 2022 Mar 4;12:831507. doi: 10.3389/fonc.2022.831507. eCollection 2022.
Ezrin and adherens junction-associated protein 1 (AJAP1) are structural proteins which are involved in numerous human malignancies. However, little is known about the relationship between them in breast cancer. This study was set out to investigate the relationship between them and to further explore the mechanism of AJAP1-mediating cytoskeleton in breast cancer progression. Ezrin and AJAP1 expressions were detected in 377 samples of breast cancer by immunohistochemistry, and different expression patterns between AJAP1 and Ezrin with clinicopathological parameters were analyzed. Besides, univariate and multivariate Cox models were used to evaluate their prognostic potential. Enzyme-linked immunosorbent assay, Western blot, qRT-PCR, and phalloidin staining of F-actin were used to explore the relationship and the mechanism between AJAP1 and Ezrin in cytoskeleton arrangement. 377 cases of breast cancer results showed that AJAP1 expression was negatively related with histological grade and lymph node involvement and could be an independent prognosis marker of breast cancer. AJAP1 expression tended to be higher in the Ezrin-negative expression case. Patients with AJAP1 and Ezrin expression had a worse prognosis ( < 0.0001) and shorter DFS ( = 0.015). More importantly, AJAP1 depletion increased the cell ability of F-actin formation through promoting Ezrin expression. AJAP1 depletion might mediate breast cancer malignancy potential through promoting Ezrin expression and cytoskeleton formation.
埃兹蛋白（Ezrin）和黏附连接相关蛋白1（AJAP1）是参与多种人类恶性肿瘤的结构蛋白。然而，在乳腺癌中它们之间的关系鲜为人知。本研究旨在探究它们之间的关系，并进一步探讨AJAP1在乳腺癌进展中介导细胞骨架的机制。通过免疫组织化学检测377例乳腺癌样本中埃兹蛋白和AJAP1的表达，并分析AJAP1和埃兹蛋白的不同表达模式与临床病理参数之间的关系。此外，采用单因素和多因素Cox模型评估它们的预后潜力。运用酶联免疫吸附测定、蛋白质免疫印迹法、实时定量聚合酶链反应以及F-肌动蛋白的鬼笔环肽染色来探究AJAP1和埃兹蛋白在细胞骨架排列中的关系及机制。377例乳腺癌病例结果显示，AJAP1表达与组织学分级和淋巴结受累呈负相关，并且可能是乳腺癌的一个独立预后标志物。在埃兹蛋白阴性表达的病例中，AJAP1表达往往更高。AJAP1和埃兹蛋白均表达的患者预后较差（<0.0001），无病生存期较短（=0.015）。更重要的是，AJAP1缺失通过促进埃兹蛋白表达增加了F-肌动蛋白形成的细胞能力。AJAP1缺失可能通过促进埃兹蛋白表达和细胞骨架形成来介导乳腺癌的恶性潜能。
