Symplekin在细胞间黏附及肿瘤发生发展中的功能研究

Symplekin是一个多功能及多细胞定位的蛋白。我们前期研究显示，symplekin在恶性病变的肝细胞中表达下调；进一步的研究结果显示，其表达降低可导致细胞紧密连接破坏、细胞极性降低、细胞周期减缓、ZO-1表达下降，且symplekin可与ZO-1形成蛋白复合体。然而，symplekin表达异常，是否可导致上皮间质转换，且分别定位于细胞膜及细胞核中的symplekin蛋白是否有一定关系，尚不清楚。在本项目中，我们将通过一系列的分子及细胞功能研究，阐明symplekin在上皮间质转换中的作用、其对ZO-1的转录调控作用及其在紧密连接复合体中的具体功能；通过有机结合研究定位于细胞膜及细胞核的symplekin相互关系,进而了解symplekin的多定位及相应功能功能。通过上述研究，我们将进一步了解symplekin在细胞间黏附及其在肿瘤发生发展中的重要作用。

Symplekin is a multi-functional protein localized in both tight junctions and nucleus. Our previous studies demonstrated decreased symplekin expression in malignant hepatocytes. Further investigations showed that repressed symplekin could lead to the failure of tight junctions, disruption of cellular polarity, and decreased expression of ZO-1, as well as that symplekin and ZO-1 could form a protein complex. However, whether abnormal expression of symplekin is involved in epithelial-mesenchymal transition, and what is the relationship between symplekin in tight junctions and nucleus, are still unclear. In this study, we intend to investigate the functions of symplekin in epithelial-mesenchymal transition and in tight juntions, as well as its transcriptional activity on ZO-1. Combined the studies on localizations and functions of symplekin, we could have a deep understanding about the interations between symplekin localized to tight junctions and nucleus. Through the above studies, we will better comprehend the roles of symplekin in cell adhesion as well as that in tumorigenesis and tumor development.