肿瘤复发和转移是影响肺腺癌患者预后的最重要因素，但其机制尚未明确。前期的实验结果发现转录辅助因子CITED4在肺腺癌中普遍高表达，并且可以预测腺癌患者的复发转移，进一步体内外实验发现CITED4水平影响肺腺癌细胞的侵袭能力，但其调控机制尚不明确，在既往的工作中发现紧密连接蛋白claudin-3是增强肺腺癌细胞的增殖及侵袭能力的关键分子，体外实验证实CITED4的表达显著影响claudin-3的水平，并初步证实CITED4能与claudin-3的结合分子CTNNB1(β-catenin)直接相互作用，本课题拟在前期工作基础上，研究CITED4在肺腺癌转移中的作用及CITED4结合β-catenin调控claudin-3水平进而影响转移的机制，在临床病例分析、细胞分子水平及动物转移模型三方面深入探讨二者的表达与肺腺癌转移和临床预后的相关性，为深入了解其调控机制及预测肺腺癌转移发现新的靶标。

Recurrence and metastasis were the most important prognostic factors for lung adenocarcinoma patients, but the underlying mechanism was not clear. Previous study had demonstrated that CBP/p300-interacting transactivator CITED4 was generally overexpression in lung adenocarcinoma, and was an important indicator for recurrence and metastasis in lung adenocarcinoma patients. The further studies had found that the expression of CITED4 affected the invasion and metastasis in vitro and vivo. These suggesting that CITED4 may play a key role in metastasis, but its regulatory mechanism was not identified. Furthermore, our previous work found that upregulation of Claudin-3 was induced the proliferation and invasion of lung adenocarcinoma cells. More importantly, the expression of CITED4 affected Claudin-3 levels significantly and suggested that CITED4 could interact directly with CTNNB1 (β-catenin), a transcription factor could bind directly to the promoter of Claudin-3 and activate its transcription. Based on the preliminary work, the role of CITED4 in the metastasis of lung adenocarcinoma and the mechanism of claudin-3 expression regulated by CITED4 binding to β-catenin would be further discussed in this topic. From the clinical specimen, cell molecular and animal model, the relationship between the CITED4 and Claudin-3 expression and lung adenocarcinoma metastasis and prognosis would be further illustrated. This study aims to gain insight into its regulatory mechanisms and find new targets for lung adenocarcinoma metastasis.