肺癌转移造成了90%以上的肺癌相关性死亡事件，其分子调控机制尚不完全清楚。申请人在国自然面上项目科学基金(No.81172214，81572276)的资助下，首次发现EHD1上调可以诱导非小细胞肺癌(NSCLC)细胞发生上皮-间质转化(EMT)并促进转移，EHD1是通过何种分子机制发挥该功能尚无文献报道。前期研究中我们应用基因芯片技术发现EHD1下调后可激活Hippo信号通路，并应用蛋白组学发现EHD1与Hippo信号通路上游调控分子CD44存在着相互作用。因此，我们推断EHD1与CD44相互作用抑制Hippo信号通路促进转移。为了证实这一假说，我们拟采用CRISPR/Cas9等分子生物学技术、裸鼠转移瘤模型，人体组织标本，研究EHD1促进NSCLC转移的分子机制及功能。本课题以新视角研究肺癌转移的生物学行为，可能为NSCLC转移的分子诊断和基因治疗提供新的理论基础。

Metastasis is the leading reason for the resultant mortality in more than 90 % of patients with lung cancer, but molecular mechanism of the lung cancer metastatic cascade remains largely unclear. Supported by grants from the National Natural Science Foundation of China(Number: 81172214, 81572276), we firstly find EHD1 promotes metastasis in non-small cell lung cancer by inducing epithelial-mesenchymal transition. But its mechanism has not been elucidated. Using microarray, we have discovered that with EHD1 knockdown Hippo signaling pathway is activated in NSCLC cells. By proteomics approach, CD44, an upstream molecular of the Hippo signaling pathway, interacts with EHD1. We hypothesized that EHD1 interacts with CD44 to regulate metastasis of non-small cell lung cancer via Hippo signal pathway. Therefore, we are planning to study the function and mechanism of EHD1 regulating NSCLC metastasis, by means of molecular biology technology including CRISPR/Cas9, xenograft models and cancer tissues. This study may provide a new perspective on the biologic behaviors of metastatic lung cancer and a new theoretical basis in molecular diagnosis and gene therapy for NSCLC patients.