基于微流控芯片技术的EphB4调控乳腺癌干细胞EMT的研究

项目名称： 基于微流控芯片技术的EphB4调控乳腺癌干细胞EMT的研究

项目编号： No.81471751

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 赵作伟

作者单位： 大连医科大学

项目金额： 80万元

中文摘要： EMT是乳腺癌干细胞侵袭和转移的关键步骤，但机制不明。我们前期研究发现：上调EphB4蛋白表达可促进乳腺癌干细胞EMT过程；同时，高表达EphB4的乳腺癌干细胞中AKT和mTOR的表达水平明显上升；且EphB4还可与PTEN蛋白发生免疫共沉淀。因此我们推测：EphB4蛋白可能通过与PTEN相互作用，阻碍了PTEN对PI3K/AKT/mTOR信号通路的抑制作用，从而促进乳腺癌干细胞发生EMT。为了证明这一假设，本项目拟利用微流控芯片技术能够模拟体内三维环境的优势，构建适合乳腺癌干细胞 EMT研究的微流控芯片平台，以乳腺癌干细胞为研究对象，检测EphB4表达上调和下调等不同条件下，乳腺癌干细胞EMT和PI3K/AKT/mTOR信号通路相关因子变化，阐明EphB4对乳腺癌干细胞EMT的调控机制，为进一步通过抑制EphB4控制乳腺癌侵袭和转移提供理论依据。

中文关键词： C21_乳腺肿瘤；EphB4；转移；上皮间质化；微流控芯片

英文摘要： EMT is a key step in breast cancer stem cells invasion and metastasis, but the mechanism is still unclear. Our preliminary study showed that up regulation of EphB4 protein expression could promote the EMT process of breast cancer stem cells, the expression level of AKT and mTOR in highly expressed breast cancer stem cells are obviously elevated, and EphB4 also occured co-immunoprecipitation in the breast cancer stem cells with PTEN protein. Therefore, we hypothesized that the EphB4 protein may block the inhibition of PTEN on PI3K/AKT/mTOR pathway by interaction with PTEN protein thereby contributing to the induction of EMT process of breast cancer stem cells. To demonstrate this suppose, based on the superiority of the micro-fluidic chip technology in simulate the three-dimensional environment in vivo, we intend to construct the micro-fluidic chip platform to research the EMT process in breast cancer stem cells. We will detect the factors changes in EMT process and PI3K/AKT/mTOR pathway through control the expression levels of the EphB4 in breast cancer stem cells. This project is devoted to illuminate the regulation mechanism of the EphB4 in the EMT process and may contribute to the further study in the breast cancer stem cells invasion and metastasis by induction of EMT process.

英文关键词： Breast cancer;EphB4;metastasis;EMT;micro-fluidic chip