我国肺癌的发病率和死亡率高居恶性肿瘤之首，非小细胞肺癌（Non-Small Cell Lung Cancer, NSCLC）约占所有肺癌的85%，其5年生存率仅为16%，复发和转移仍是NSCLC高死亡率的重要原因。Wnt/β-catenin/Lef1信号通路在NSCLC发生与发展中高度活化，通过增强FUT8的表达而促进上皮-间质转化和NSCLC转移；另外，通过维持NSCLC干细胞休眠体的形成而促进肿瘤复发和耐药。因此，β-catenin/Lef1相互作用可能成为NSCLC分子靶向治疗的新靶点。本研究拟以β-catenin/Lef1相互作用为靶点，以FITC-Lef1作为β-catenin结合配体，建立基于荧光偏振原理的高通量筛选模型理性化发现靶向β-catenin/Lef1相互作用小分子抑制剂，并进一步探索其抑制NSCLC转移的分子机制，为其在NSCLC分子靶向治疗中的应用奠定基础。

Lung cancer is the leading cause of cancer death in China due to its aggressive clinical pathogenesis. Non-small-cell lung cancer (NSCLC), a heterogeneous class of tumors, represents approximately 85% of all new lung cancer cases. Because of a rapid distant metastasis to multiple organs within months of diagnosis, the average of 5-year survival rate for NSCLC is only 16%. Because of the shortage of effective anti-metastatic agents in NSCLC clinical practice, relapse and metastasis could greatly account for these therapeutic failures. Hyperactivation of the canonical Wnt/β-catenin/Lef-1 pathway has been to be essential for metastasis to brain and bone during NSCLC progression. Importantly, fucosytransferase 8 (FUT8) is greatly up-regulated during epithelial-mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via trans-activation of β-catenin/Lef1 signaling. Moreover, this signaling pathway contributes to promote NSCLC recurrence and resistance by maintaining cancer stem cells (CSC) dormancy. Therefore, suppressing β-catenin/Lef1 signaling pathway is an important anti-metastatic strategy for NSCLC therapeutics. In this study, we will use FITC-Lef1 as β-catenin aptamer to first develop a fluorescence polarization-based high throughput screening (HTS) method to identify novel antagonists specially targeting β-catenin/Lef1 interaction. Furthermore, we will further elucidate the molecular basis for the anti-metastatic effect using a cell-based assay and xenograft nude mice. Our proposed research is expected to shed light on the development of novel antagonists targeting β-catenin/Lef1 interaction for NSCLC therapeutics by inhibiting metastasis.