TIP60调控Septin7相变介导胃上皮细胞极性建立分子机制研究

组织或器官正常生理状态的维持需要上皮细胞顶膜与底膜极化特性的正确建立，极化特性的紊乱与丧失是导致上皮细胞肿瘤的重要原因。Septin7是细胞内第四种骨架蛋白，参与调控细胞有丝分裂，细胞迁移等多种生物学过程。生物信息学预测数据说明，Septin7蛋白具有高潜能的相变特性。我们最新研究揭示了上皮细胞极化过程中Septin-catenin复合物的存在，为阐明Septin7的细胞动力学机制奠定了基础。我的近期工作建立了具有极性特征的胃类器官模式体系并成功解析了幽门螺杆菌致病机制。为此，我拟集成超高分辨率显微镜成像与三维类器官的模式体系优势，探究Septin7蛋白相变特性在胃上皮细胞极性形成的分子机制，为解析Septin7功能变异导致细胞极性紊乱所致胃癌的发生发展提供新视角与技术平台。

The maintenance of normal physiological state of tissues or organs requires the correct establishment of polarization characteristics of apical and basal membranes of epithelial cells. The disorder and loss of polarity is an important cause of epithelial tumor. Septin7 is the fourth skeleton protein, which is involved in the regulation of mitosis, cell migration and other biological processes. Bioinformatics data indicated that Septin7 protein had high potential for phase separation. Our latest study reveals the presence of Septin-catenin complex in the polarization process of epithelial cells, which lays a foundation for understanding the cellular dynamics of Septin7 protein. My recent work has established a model system of gastric organoids with polarization and successfully analyzed the pathogenesis of Helicobacter pylori using human gastric organoids. Therefore, we plan to combine the advantage of 3D organoids with high resolution microscope to reveal the detailed mechanism of Septin7 phase separation in regulating gastric epithelial cell polarity formation. It provides a new perspective and technical platform for analyzing Septin7 functional variation to the occurrence and development of gastric cancer.