TIP30基因是与肿瘤密切相关的抑癌基因。TIP30蛋白可分布在细胞核、核膜和胞浆内，通过多个环节调节细胞生长和凋亡。我们以往的研究已证明TIP30可通过调节EGFR的胞浆内转运、降解和核内化，抑制EGFR信号通路激活。最近我们又发现EGF可诱导TIP30核内化，但TIP30如何在细胞内不同部位转运、如何跨核膜转运、EGF如何诱导TIP30核内化、核内的TIP30是否参与EGFR核内信号的负反馈调节等目前还不清楚。本项目拟用免疫共沉淀、染色体免疫共沉淀、激光共聚焦等方法，探索EGFR信号通路如何调节TIP30核内化、TIP30如何通过核膜、核内的TIP30对EGFR核内信号的调节作用及TIP30是否与靶向EGFR药物的敏感性相关等问题。初步阐明TIP30细胞内转运的分子机理，进一步了解TIP30的生理功能和相关调节机制，并探索TIP30作为靶向EGFR药物的新的疗效预测指标的可能性。

TIP30 is a tumor suppressor which can regulate cell proliferation and apoptosis through several mechanisms in the nuclear or plasma of cells. We have found that TIP30 knockdown can prolong the activity of EGFR downstream signaling through down-regulate EGFR endocytosis and degradation, and increase EGFR nuclear localization.Our previous data also has shown that EGF treatment can induce TIP30 nuclear localization. However, how EGF treatment can induce TIP30 nuclear localization,and the corelation of TIP30 with EGFR nuclear signaling is still unknown. In addition, how TIP30 can transport through nuclear membrane to nuclear is also not clear. In this study, we aim at exploring why EGFR signaling pathway can regulate TIP30 nuclear localization , and how TTP30 can transport through nuclear membrane by using IP, CHIP and Confocal-microscopy. Moreover, we also want to further clarify whether TIP30 could?be as a predictive marker for EGFR-targeted therapy in human lung adenocarcinoma.