FRAT1对胶质瘤干细胞的调控作用及机制研究

项目名称： FRAT1对胶质瘤干细胞的调控作用及机制研究

项目编号： No.81201991

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： 郭庚

作者单位： 山西医科大学

项目金额： 23万元

中文摘要： 胶质瘤干细胞因其极强的致瘤特性和对放化疗的抵抗性，被视为胶质瘤的根源和潜在的治疗靶点。FRAT1是Wnt/β-catenin信号转导通路的重要成员，研究表明它是一个在肿瘤增殖和侵袭中有着重要作用的基因。本课题组前期研究显示，FRAT1在脑胶质瘤中高表达，其表达水平随胶质瘤病理级别的升高而增高；下调FRAT1表达能够抑制脑胶质瘤细胞的增殖和侵袭。我们还发现FRAT1在胶质瘤干细胞中高表达且与CD133在胶质瘤干细胞中存在共定位现象。本研究将在前期工作的基础上，分析FRAT1在胶质瘤干细胞中的表达，系统探讨FRAT1对胶质瘤干细胞的生物学特性的影响，进而研究FRAT1影响胶质瘤干细胞的可能分子机制。从而为全面理解FRAT1这一癌基因的功能及胶质瘤的形成机制提供依据，同时建立针对FRAT1的胶质瘤干细胞干预措施，为胶质瘤的临床治疗提供新的思路。

中文关键词： FRAT1；脑胶质细胞瘤；胶质瘤干细胞；增殖；分化

英文摘要： The cancer stem cell (CSC) hypothesis suggests that glioma is driven by a subpopulation of glioma stem cells (GSCs) which also contributes to their resistance to therapy. Therefore, it is important for both research on cancer and clinical practice to further explore the intrinsic molecular basis beneath the tumorigenicity of GSCs. FRAT1 is a core component of the Wnt/β-catenin pathway, FRAT1 has been identified as a proto-oncogene involved in tumorigenesis. Previous studies have shown that FRAT1 is strikingly overexpressed in several human cancers including esophageal cancer, cervical cancer, breast cancer, ovarian cancer, and so on. We found that FRAT1 was highly expressed in most subtypes of gliomas and the expression levels of FRAT1 were significantly positively correlated with increasing WHO grades. The results also suggested that FRAT1 protein expression was positively correlated with tumor proliferation. Furthermore, RNAi targeting FRAT1 can suppress proliferation and invasion of human brain glioma cells in vitro and in vivo. Our previous study found that FRAT1 and stem cell marker CD133 showed co-expression in GSCs. Moreover, FRAT1 mRNA and protein were highly expressed in GSCs. On the basis of precedent researches, this study will investigate the expression of FRAT1 in GSCs, explore the FRAT1 effect on b

英文关键词： FRAT1；glioma；glioma stem cells；proliferation；differentiation