转移是肺癌难以治愈的重要原因之一，阐明肺癌转移的分子机制对肺癌转移预测以及干预治疗有十分重要的研究意义。分区缺陷蛋白 3（Par3）是细胞极性蛋白，在细胞运动和维持细胞极性方面起着重要作用。多种致癌基因的表达能促使 Par3 蛋白丢失，导致细胞运动能力增强。对此我们进行了前期研究：过表达 p53 突变体（R175H），Par3 蛋白表达下调，且肺癌细胞的迁移能力也随之增强；沉默 Par3 基因肺癌细胞迁移能力增强；利用 oncomine 数据库分析发现在肺癌和乳腺癌组织中 Par3 的表达明显下降。基于以上结果，我们推测 Par3 的丢失与肺癌的转移密切相关。本项目拟在前期研究工作的基础上，针对 Par3 信号途径在 R175H 诱导肺癌转移中的作用，并详细阐述 R175H 调控 Par3 蛋白的分子机制，同时在裸鼠模型上验证 Par3 的抗肿瘤效力。

Metastasis is one of the most important reasons for the treatment of lung cancer. Clarifying the molecular mechanism of lung cancer metastasis is of great significance for the prediction and intervention therapy of lung cancer metastasis . The partitioning defective protein 3（Par3）of cell polarity proteins, was identified as regulators of cell-cell junction, asymmetric cell division and cell migration during early embryonic development. Our previous study showed that the expression of the oncogene cause the loss of Par3 protein. Here, we investigated mutant p53 protein (R175H) in regulation of cell migration and invasion. Futher study demonstrated that R175H downregulation of Par3 to promote cell miagration. In addition, knockdown of Par3 with lentivirus significantly promoted cell migration and invasion, and the downstream target gene SNAIL of Par3 protein was down regulated accordingly. To further explore clinical relevance of Par3 expression in human cancer specimen, analysis of oncomine Database showed that the expression of Par3 significantly decreased in human lung cancer and breast cancer specimens. Hence, we speculate that the loss of Par3 is closely related to the metastasis of lung cancer. Therefore, this project aim to study the role of Par3 protein in R175H induced lung cancer metastasis, elaborate the molecular mechanism of R175 regulating Par3 protein, and verify the anti-tumor potency of Par3 in nude mice.