DNA-PKcs-APC/C-ID1通路在肿瘤转移中的功能与机制研究

项目名称： DNA-PKcs-APC/C-ID1通路在肿瘤转移中的功能与机制研究

项目编号： No.81502583

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： 李兵

作者单位： 中国人民解放军联勤保障部队第九四〇医院

项目金额： 18万元

中文摘要： 肿瘤转移在肿瘤引起的死亡中占很大比重，肿瘤干细胞是肿瘤转移的关键因素。DNA-PKcs缺陷与多种肿瘤的转移性相关，但其具体机制目前尚不清楚。我们的前期工作发现DNA-PKcs参与泛素连接酶复合物APC/C的调控，APC/C调控着细胞干性调控关键因子ID1蛋白稳定性，据此我们提出假设，DNA-PKcs通过APC/C-ID1通路参与肿瘤干细胞及血管内皮祖细胞调控，进而影响肿瘤转移。本项目将采用实时定量PCR、免疫蛋白印迹、免疫共沉淀、慢病毒载体转染、RNA干扰、免疫荧光、动物模型等手段，从分子、细胞和动物整体水平等多方面探讨DNA-PKcs在肿瘤干细胞调控及其介导的肿瘤转移中的重要作用，明确DNA-PKcs缺失引起肿瘤转移的具体机制。本研究将拓展现有对肿瘤干细胞调控的认识，丰富对DNA-PKcs功能的理解，为优化肿瘤治疗与抑制肿瘤转移提供理论依据及潜在靶点。

中文关键词： 肿瘤转移；肿瘤干细胞；血管生成

英文摘要： Cancer stem cells play a important role in matastasis which take a great proportion of death caused by tumors. Although the deficiency of DNA-PKcs is associate with cancer matastasis in many cell types, the mechanism involved is yet well understood. Our previous works demonstrated that DNA-PKcs participate in the regulation of ubiquitine ligase complex APC/C which control the ID1' stability. ID1 is a key regulator of stem cells' stemness, and then we assume that DNA-PKcs regulate cancer stem cells and endothelial progenitor cells through APC/C-ID1 pathway and then impact tumor matastasis. This program will study the functions of DNA-PKcs in cancer stem cells and they mediated matastasis at molecular, cellular and creatural levels by utilizing the methods of real-time PCR, western blot, co-IP, lentivirus vector transfer, RNA interference, immunofluorescence and animal model. This study will expand our knowledge about cancer stem cells' regulation and the functions of DNA-PKcs, providing theoretical support and potential targets for cancer therapy optimizing.

英文关键词： cancer matastasis;cancer stem cell;angiogenesis