泛素连接酶Nedd4-1在肺癌组织中高度表达，但其在肺癌发生和发展中的作用仍不清楚。我们的近期工作发现泛素连接酶Nedd4-1在肺癌细胞中与激活的表皮生长因子受体（EGFR）形成复合物，调节其内吞体的转运及信号。 RNAi敲除Nedd4-1导致EGF促肺癌细胞迁移的效应显著降低，表明Nedd4-1在肺癌细胞中介导EGFR的促细胞迁移信号。本课题拟在肺癌细胞中对Nedd4-1 介导的EGFR内吞体信号及促细胞迁移信号从分子和细胞水平上进行系统的分析研究，确定Nedd4-1在EGFR内吞体信号转导中的作用以及该内吞体信号与肺癌细胞迁移的因果关系。同时，我们还将测定Nedd4-1在肺癌样品中的表达，确定Nedd4-1的过表达与肺癌发生和发展过程的关联性。通过这些研究，我们期望能进一步理解肺癌发生和发展的分子机理，为肺癌的靶向治疗提供新的理论基础。

Overexpression of the E3 ubiquitin ligase Nedd4-1 has been observed in lung cancer. However,the role of Nedd4-1 in lung tumorigenesis and progression remains elusive. Our preliminary studies have shown that Nedd4-1 interacts with epidermal growth factor receptor (EGFR) in lung cancer cells upon EGF stimulation, regulates endosomal trafficking of EGFR and mediates EGF-promoted lung cancer cell migration. This project is to elucidate the molecular mechanism by which Nedd4-1 regulates EGFR endosomal signaling and delineate the Nedd4-1-mediated EGFR cell migration signal pathway in lung cancer cells. Furthermore, we will examine the expression of Nedd4-1 in human lung tumor samples by immunohistochemical(IHC) staining and determine the correlation between overexpression of Nedd4-1 with lung tumor grade, stage, type, metastasis, and prognosis. From the studies, we will forward our understanding of the molecular mechanism underlying Nedd4-1-mediated lung tumorigenesis and progression, establish Nedd4-1 as a diagnostic marker of lung cancer progression and validate Nedd4-1 as a target molecule in lung cancer therapy.