I型干扰素抑制肿瘤转移的功能与分子机制研究

项目名称： I型干扰素抑制肿瘤转移的功能与分子机制研究

项目编号： No.81472665

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： 徐平龙

作者单位： 浙江大学

项目金额： 75万元

中文摘要： 肿瘤转移是引起癌症患者死亡的首要因素（90%），其发生涉及到多层面因素，具有较强的可干预性，也是当前生物医学领域的国际前沿和热点问题。I型干扰素是宿主天然免疫应答的主要产物之一，也是当前临床上应用广泛的病毒和肿瘤治疗药物。近年来的研究逐步表明I型干扰素可能参与调控了肿瘤转移的某些关键进程，但其作用机理还不甚清楚。申请人的预实验表明，I型干扰素能够通过诱导IRF7蛋白，有效抑制在肿瘤转移和免疫中起关键功能的TGF-beta信号通路。本研究项目将围绕I型干扰素抑制肿瘤转移的功能与机制这一关键科学问题，从基因表达、信号通路控制、细胞分化和动物模型等多方位研究I型干扰素控制肿瘤转移的分子网络和信号通路的变化规律，以及关键蛋白分子在肿瘤转移过程中的新功能。本项目内容充分兼顾了重要科学问题与国家实际需求，将有助于我们深入理解肿瘤转移的分子机制，并为干预和抑制肿瘤转移这一癌症防治策略提供理论依据与药物靶点。

中文关键词： 肿瘤转移；蛋白质修饰；I型干扰素；转化生长因子β；细胞信号传导

英文摘要： Metastasis accounts for 90% of cancer death. Metastasis prevention is therefore a crucial scientific issue and also the frontiers in current biomedical research. Type I IFNs, sourced from response of innate host defense, is one of primary types of medicine for cure of cancer and viral diseases. Recent studies indicated it may participate in the regulation of a few key processes of cancer metastasis, though very little is known about its underlying mechanism. At the same time, pilot studies in applicant's laboratory implied that type I IFNs, through its induction of IRF7 protein, blocks the activation of TGF-? pathway that is critical in metastasis regulation. This proposed study is therefore focusing on type I IFNs-mediated regulation of cancer metastasis to investigate its molecular network and regulation dynamics, via distinct scientific views of gene expression, signaling pathway, cell differentiation, and animal model. The study pays attentions to both the critical scientific issue and demands of national interest. The knowledge gained from this study will shed light on the mechanism of cancer metastasis, and also, to present evidence for potential target of drug development.

英文关键词： Metastasis;Protein Modification;Type I Interferon;TGF-β;Signal Transduction