Hedgehog/Gli1信号通路调控EMX2表达在肺鳞癌EMT转化和侵袭转移过程中的作用及机制研究

项目名称： Hedgehog/Gli1信号通路调控EMX2表达在肺鳞癌EMT转化和侵袭转移过程中的作用及机制研究

项目编号： No.81501983

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 岳东升

作者单位： 天津医科大学

项目金额： 18万元

中文摘要： 肿瘤侵袭和转移是影响肺鳞癌预后的主要因素，而上皮间质转化（EMT）则可能是侵袭、转移的关键机制。Hedgehog（Hh）信号通路关键分子Gli1及下游的EMX2均与肿瘤的侵袭转移过程密切相关。我们前期研究发现Hh/Gli1在肺鳞癌中异常激活，而阻断Gli1可能抑制肺鳞癌细胞的迁移侵袭，但机制不清；最近研究发现Hh/Gli1能够调控EMX2的表达，我们前期研究显示EMX2在肺鳞癌中表达下调，过表达EMX2则可抑制肺鳞癌细胞的EMT转化和迁移侵袭。据此我们提出“Hh/Gli1通路通过调控EMX2表达，促进肺鳞癌发生EMT转化及侵袭转移”这一研究假说。为此，本课题拟通过激活和阻断Hh/Gli1通路活性，并结合干扰Gli1和EMX2表达，分析Hh/Gli1通路对EMX2的调控机制，揭示Hh/Gli1-EMX2通路在肺鳞癌EMT转化和侵袭转移过程的作用及机制，从而为肺鳞癌的治疗提供新靶点和新策略。

中文关键词： 肺肿瘤；Hedgehog；信号通路；空通气孔同源盒2；上皮间质转化；侵袭与转移

英文摘要： Tumor invasion and metastasis correlate with poor prognosis of lung squamous cell carcinoma (LSCC), and Epithelial-Mesenchymal Transition (EMT) has been implicated in the process. Preliminary data suggested that the Hedgehog signaling pathway (Hh) as well as its downstream factor EMX2 may regulate tumor invasion and metastasis. Our results suggested aberrant activation of Hh signaling pathway as well as decreased expression of EMX2 in LSCC correlate with EMT, invasion and metastasis; inhibition of EMX2 stimulated EMT, invasion and metastasis, while elevated expression of EMX2 suppressed these processes. Therefore, we proposed the hypothesis that Hh/Gli1 signaling pathway may promote EMT, invasion and metastasis via regulating EMX2 transcription and expression. To investigate the mechanism of Hh/Gli1-EMX2 in EMT, invasion and metastasis in LSCC, activation and inhibition of the Hh pathway, as well as antagonism of Gli1 and EMX2 will be utilized in the study. The current study is expected to reveal the mechanism of the Hh/Gli1 pathway and its downstream factor EMX2 in regulating cell invasion and metastasis, and may provide insights that lead to potential therapeutic targets and strategies of LSCC.

英文关键词： Lung cancer;Hedgehog signal pathway;Empty spiracles homeobox 2;EMT;Invasion and metastasis