以TRAF6为核心的分子网络对肿瘤干细胞的调控及其靶向治疗策略的探索

项目名称： 以TRAF6为核心的分子网络对肿瘤干细胞的调控及其靶向治疗策略的探索

项目编号： No.81502562

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： 陈翀

作者单位： 中国医学科学院基础医学研究所

项目金额： 19万元

中文摘要： 大量研究证明炎性通路的激活能够维持肿瘤干细胞的自我更新能力，但其分子机制并不十分清楚。我们利用siRNA文库对1027个炎性相关基因进行筛选，首次发现炎性分子TRAF6能够调控肿瘤干细胞的自我更新能力，其分子机制可能是通过激活IKKβ/NFκB和ERK/Fra-1信号通路从而上调干性分子LIN28B的表达。接下来我们计划深入研究TRAF6及其分子网络对肿瘤干细胞的调控机制和靶向治疗的探索：1）明确TRAF6与临床肿瘤进展的关系；2）利用siRNA文库系统研究受TRAF6调控的激酶及其在肿瘤干细胞中的功能；3）探讨TRAF6在肿瘤细胞核内的功能；4）利用纳米载体靶向治疗策略阻断TRAF6及其分子网络对肿瘤干细胞的支持，从而抑制肿瘤的生长和转移。本研究的目的和意义在于从分子水平阐明抑制关键炎性分子及其网络节点能够抑制肿瘤干细胞从而抑制肿瘤，为肿瘤治疗提供新的理论依据。

中文关键词： 肿瘤干细胞；慢性炎症；TRAF6；肿瘤转移；靶向治疗

英文摘要： Substantial evidence indicates that activation of the inflammatory pathways drive the self-renewal of cancer stem cells (CSCs); however, the molecular basis of this process remains undefined. Among the 1027 inflammatory related genes, TRAF6 was firstly recognized as a regulator of CSCs by our siRNA library screening. Expression of LIN28B was up-regulated by activated IKKβ/NFκB and ERK/Fra-1 signaling pathways which were regulated by TRAF6. We plan to investigate the roles of TRAF6 and its network in the functional regulation of cancer stem cells and feasibility of the targeted therapy: 1) to demonstrate the relationship between TRAF6 expression and cancer progression; 2) to search the key kinase regulated by TRAF6 with using siRNA library; 3) to investigate the roles of TRAF6 in cell nucleus; 4) to block the support of TRAF6 and its network for CSCs by targeted treatment, thus inhibiting tumor growth and metastasis. This study was aimed to elucidate the molecular mechanism that blocking key inflammatory molecules in CSCs could suppress cancer progression and provide a new theoretical basis for cancer treatment.

英文关键词： cancer stem cell;inflammation;TRAF6;metastasis;targeted therapy