RhoGDI2用于肺癌临床预后评估及参与侵袭转移分子机制的研究

项目名称： RhoGDI2用于肺癌临床预后评估及参与侵袭转移分子机制的研究

项目编号： No.81201832

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 牛慧彦

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： RhoGDI2作为肿瘤转移相关因子，其在肺癌转移中的具体的作用机制及其调控机理尚不清楚。前期研究我们发现RhoGDI2在大多数肺癌组织中的表达低于相对应的正常组织，并首次报道肺癌细胞中RhoGDI2与PI3K/Akt信号通路存在密切的内在联系。在此工作基础上，本课题将扩大肺癌的临床标本量，进一步证实RhoGDI2在肺癌患者预后判断中的价值；在肺癌细胞株过表达或沉默RhoGDI2，通过正反两方面的干预，利用体内外实验明确RhoGDI2在肺癌侵袭及转移等恶性生物学特征中的作用，并深入探讨其参与肺癌细胞侵袭转移过程中的可能机制；进一步证实RhoGDI2与PI3K/Akt信号通路之间的调控关系。本项目完成旨在为肺癌的诊断和预后判断，及肿瘤的临床治疗提供新的靶点。

中文关键词： 鸟嘌呤核苷酸解离抑制因子2；转移；侵袭；上皮间质转化；

英文摘要： RhoGDI2 has been shown to be a metastasis regulator, however, the underlying mechanism, effector targets, and the cognate biological functions of RhoGDI2 are not fully understood in lung cancer. In previous studies, we found that the protein expression of RhoGDI2 was lower in lung cancer tissues than normal lung tissues, a result that, for the first time, points to the direction that RhoGDI2 may interact with the PI3K/Akt pathway. Based on our data, we propose to increase the number of the studied samples with lung cancer from 112 to 300 in order to further verify the clinical value of RhoGDI2 expression in the prognosis of lung cancer. In addition, we will identify the biological function of RhoGDI2 in the invasion and metastasis of lung cancer by in vivo and in vitro experiments and further investigate the key underlying molecular mechanisms involving RhoGDI2 in lung cancer. Finally, we will verify and functionally dissect the potential interactions between RhoGDI2 and the PI3K/Akt pathway. Our study may provide a new target for the diagnosis, prognosis and treatment of the more treatment-refractory form of lung cancer.

英文关键词： RhoGDI2；metastasis；invasion；EMT；