表皮生长因子酪氨酸激酶抑制剂（EGFR-TKI）对EGFR突变的非小细胞肺癌凸显疗效，而TKI的获得性耐药使其应用陷入瓶颈，故颇受关注。我们前期研究发现：在肺癌组织中RNA结合基序蛋白5（RBM5）与EGFR的表达呈负相关；导入外源性RBM5 可下调β-catenin（Wnt经典通路的关键基因）的表达。也有研究表明EGFR与Wnt/β-catenin 存在交叉通路，且与TKI获得性耐药密切相关。故我们推测：向肺腺癌细胞中导入外源性RBM5可以通过抑制EGFR和Wnt/β-catenin信号通路延缓或逆转TKI耐药。本研究将在人肺癌细胞系、动物移植瘤模型中，联合采用RBM5基因导入、β-catenin通路阻滞剂干预，来明确RBM5与EGFR、Wnt/β-catenin通路之间调控关系，明确TKI获得性耐药发生和逆转的分子机制，为临床非小细胞肺癌靶向治疗的发展提供科学依据。

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is one of the targeted agent with preferable clinical benefit to certain type of non-small cell lung cancer (NSCLC). However, the TKI acquired resistance is the key factor to limit its curative effect,which becomes the focus that scholars pay close attention to. Our previous studys showed that, the expression of RBM5 and EGFR was negatively correlated in lung cancer tissues, and transformation of exogenous RBM5 could down-regulate the expression of β-catenin,which is the key gene of classic Wnt pathway. Studes demonstrated that the application of inhibitors of β-catenin signaling pathway was able to reverse the resistance of TKI. Therefore, we make the following hypothesis: the transformation of exogenous RBM5 in tumor cells could delay or reverse TKI resistance through the inhibition of Wnt signaling pathway.Thus,in this study, we will carry on a further research, with the intervention of RBM5 transformation/knockout and inhibitors of β-catenin signaling pathway, to investigate the regulation between RBM5, EGFR signal pathway, and Wnt/ β-catenin signal pathway and the mechanism of TKI acquired resistance and reversal. And it will provide the scientific basis and targets for the development of non small cell lung cancer targeted therapy clinically.