前期研究发现，非小细胞肺癌患者体内PLGF显著升高且与肿瘤转移呈正相关，PLGF能通过Flt-1激活肿瘤相关巨噬细胞（TAMs），诱导TGFβ的释放刺激内皮细胞，最终促血管新生和肿瘤转移。芯片分析发现E-cadherin是PLGF的负向调控因子，已知E-cadherin糖基化修饰能增强其与β-catenin结合并抑制β-catenin入核而抑制肿瘤恶化。由此推测非小细胞肺癌中可能存在E-cadherin/β-catenin/PLGF信号轴调控肿瘤发生发展。我们将检测临床样本中E-cadherin /β-catenin/PLGF的表达相关性；利用CRISPR/Cas9高通量筛选分析PLGF启动子/增强子分布，揭示E-cadherin和β-catenin调控PLGF表达的机制，进一步研究E-cadherin /β-catenin/PLGF信号轴对非小细胞肺癌发生发展的影响，以探索其诊疗新靶标。

Our previous study showed that PLGF expression in non-small cell lung cancer (NSCLC) tissues was significantly higher than that in adjacent normal tissues. PLGF could stimulate tumor-associated macrophages (TAMs) via Flt-1 to induce the secretion of TGFβ, which subsequently stimulate endocrine cells to promote angiogenesis and tumor metastasis. Microarray analysis revealed that PLGF was negatively regulated by E-cadherin in NSCLC cells. It has also been reported that E-cadherin exerts tumor suppressing roles by interacting with β-catenin to inhibit its nuclear accumulation. Furthermore, it is known that glycosylation enhanced the interaction between E-Cadherin and β-catenin, further inhibiting the nuclear functions of β-catenin and tumor progression. So we proposed that E-cadherin/β-catenin/PLGF axis existed in NSCLC and was essential for its initiation and progression. In this project, we will examine the expression status of E-cadherin, β-catenin and PLGF and their relationship in NSCLC. Then high-throughput CRISPR/Cas9 screening will be used to identify PLGF promoter and enhancer locus and to explore the molecular mechanisms underlying PLGF expression regulation by E-cadherin/β-catenin. The impact of E-cadherin/β-catenin axis on PLGF expression and NSCLC initiation and progression in vitro and in vivo will be further investigated here to provide novel targets for NSCLC prognosis and treatment.