中心体蛋白MPP9在纤毛去组装过程中的分子机制及其功能研究

初级纤毛是突出于细胞表面特化的细胞器，其生长调节（组装/去组装）失控导致的多种信号通路转导异常与肿瘤的发生发展密切相关。相对于纤毛组装过程，纤毛去组装的分子机制还有很多问题尚未阐明。进一步深入了解纤毛去组装的分子机制以及其与肿瘤发生发展的关系具有重要意义。我们前期的研究发现MPP9在起始纤毛组装过程中发挥重要的负调控作用，后续研究进一步发现MPP9也能促进纤毛去组装，然而其分子机制以及MPP9在肿瘤发生发展中的作用还不清楚。因此，本项目拟采用定量蛋白质组学技术等分子细胞生物学手段鉴定MPP9在纤毛去组装过程中的相互作用蛋白，阐明MPP9促进纤毛去组装的分子机制；并通过体内/外实验进一步完成对MPP9的功能研究，明确其在肿瘤发生发展中的作用。本项目的实施将使我们对纤毛去组装的分子机制以及纤毛去组装与肿瘤发生发展的关系有更加全面和深入地了解，为肿瘤疾病患者的诊疗提供新的思路和理论依据。

Primary cilia are specialized organelles that protrude on the cell surface. Abnormal transduction of signal pathways resulted from uncontrolled cilia growth including cilia assembly and disassembly, are closely related to tumorigenesis and tumor progression. Compared with the process of cilia assembly, there are still many unsettled issues in cilia disassembly. It is of great significance to further understand the underlying mechanism of cilia disassembly and the relationship between cilia disassembly and tumor. Recently, we have found that MPP9 negatively regulates the initial cilia assembly process. Furthermore, we preliminarily find that MPP9 can also promote cilia disassembly. However, the underlying mechanism and its role in cell proliferation and tumor have not been addressed. We initiate the current study to identify the interacting proteins of MPP9 during cilia disassembly by quantitative proteomics, and then clarify the unknown mechanism of MPP9 by using molecular cell biological method. Finally, we attempt to confirm the role of MPP9 in tumor occurrence and development by in vivo and vitro study. This project will enable us to have a more comprehensive and in-depth understanding of the molecular mechanism of cilia disassembly and its relationship with tumor, providing new ideas and theoretical basis for the diagnosis and treatment of patients with tumor.