转录因子Ikaros在抑制肝癌干细胞增殖中的功能和分子机制研究

项目名称： 转录因子Ikaros在抑制肝癌干细胞增殖中的功能和分子机制研究

项目编号： No.81472726

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： 李锦军

作者单位： 上海交通大学

项目金额： 72万元

中文摘要： 肿瘤干细胞是导致恶性肿瘤的复发、转移与不良预后以及恶性肿瘤化疗失败的主要原因。利用肿瘤干细胞的分子标记物设计新型肿瘤治疗新策略对克服肿瘤的化疗抗性、获得有效化疗方案具有重要意义。肝癌是我国发病率和死亡率均很高的一种恶性肿瘤，其化疗效果、预后均很差。本项目旨在我们前期研究为基础上，开展以下三个方面的研究：（1）揭示转录因子Ikaros在肝癌干细胞增殖中的功能；（2）阐明转录调控因子Ikaros通过调节肝癌干细胞标志物CD133、EpCAM等的表达对肝癌干细胞自我更新、分化的体内外增殖发挥影响；（3）提出基于转录因子Ikaros的实验性肝癌干细胞靶向治疗策略，着重研究Ikaros过表达对降低CD133、ABCG2等蛋白糖基化为基础的肝癌干细胞靶向治疗。该研究成果将为肝癌干细胞靶向临床肝癌治疗方案的制订提供重要的实验依据和必要的理论指导。

中文关键词： C09_肝和肝内胆管肿瘤；癌干细胞；转录因子Ikaros；分子机制

英文摘要： Cancer stem cells (CSCs) are one of the main reasons to lead to cancer recurrence, metastasis and poor prognosis as well as failure of anticancer radiotherapy and chemotherapy. Therefore, based on biomarkers of CSCs to develop HCC CSC-targeting chemotherapeutic strategy will contribute to overcome the multidrug resistance and to find an effective chemotherapy regimen. Hepatocellular carcinoma (HCC) is a malignant cancer with very high morbidity and mortality in China, which also has poor chemotherapeutic effect and poor prognosis. Based on our preliminary studies, we will focus on the following research fields: (1) to clarify the function of transcription factor Ikaros in HCC CSCs; (2) to be clear how transcription factor Ikaros to affect the self-renewal and differentiation of HCC CSCs through regulating the expression of biomarkers of HCC CSC biomarkers CD133, EpCAM etc in vitro and in vivo; (3) to develop a novel strategy of experimentally targeting HCC CSC chemotherapeutics, especially, HCC CSC-targeting chemotherapy based on Ikaros overexpression induced deglycosylation of glycoproteins (CD133 and ABCG2) in vivo. This study will provide an important experimental basis and the necessary theoretical guidance to HCC clinic for targeting HCC CSCs.

英文关键词： HCC;Cancer stem cell;Ikaros;Molecular mechanism