HGF/Met通过表观调控SNAIL1促进非小细胞肺癌转移的分子机制研究

癌症转移是非小细胞肺癌（NSCLC）治疗失败和死亡的重要原因。本课题组研究发现肝细胞生长因子HGF能够激活受体Met发生裂解产生胞内片段Met-ICD，并促进SNAIL1的表达和上皮-间质化（EMT）的发生。同时，还发现Met-ICD能够与组蛋白去甲基化酶LSD1结合并影响组蛋白的甲基化修饰。因此，围绕“NSCLC转移的分子调控机制”这一关键科学问题，提出假说“Met-ICD通过与LSD1形成复合物来表观调控SNAIL1基因的表达，从而促进EMT和转移”。本项目将围绕Met-ICD/LSD1复合物调控EMT和转移的分子机制展开研究，探讨Met-ICD与LSD1形成复合物并影响SNAIL1组蛋白甲基化的调控机制，观察Met-ICD/LSD1复合物对EMT和转移的影响，并分析Met-ICD与NSCLC转移的临床相关性。本项目的研究结果将为阻断、控制和治疗NSCLC转移提供新的理论和方法。

Cancer metastasis is the important reasons for the treatment failure and death of non-small cell lung cancer (NSCLC). We have been found that HGF/Met were associated with NSCLC metastasis. HGF can activate Met to be fractured into intracellular fragment Met-ICD, and promote the expression of SNAIL1 resulting in EMT and metastasis of NSCLC cells. Furthermore, we also found that Met-ICD can bind with LSD1 to formed Met-ICD/LSD1 compounds and affect the methylation of histone. Therefore, this project is based around the key scientific problem of ‘the molecular regulatory mechanism of NSCLC metastasis’, suggesting that ‘Met-ICD regulate the expression of SNAIL1 through forming compounds with LSD1, thus inducing EMT and metastasis of NSCLC cells’. This project will research the molecular mechanism of Met-ICD/LSD1 compounds in regulating the EMT and metastasis of NSCLC cells, explore the regulatory mechanism of forming Met-ICD/LSD1 complexes and histone methylation of SNAIL1, analysis the impact of Met-ICD/LSD1 compounds in the EMT and metastasis of NSCLC cell, and verify the clinical relevance between Met-ICD and NSCLC metastasis. The project results will offer new theory and method for blocking, controlling, and therapy of NSCLC metastasis.