IL-6/STAT3信号转导调控网络与炎-癌转化研究

This project is in response to the Call for Proposals entitled “Signaling by the interleukin family members and inflammation-mediated tumorigenesis”. Previously, it has been demonstrated that chronic or unresolving inflammation is critically involved in tumorigenesis. IL-6-STAT3 signaling plays an important role in this process. In our preliminary studies, we performed expression screens from ~13000 human and murine cDNA clones for candidate proteins involved in IL-6-STAT3 signaling by reporter assays. This led to the identification of 119 candidate proteins. In this project, we will confirm whether these candidate proteins are specifically involved in IL-6-STAT3 signaling; we will elucidate the molecular mechanisms of these candidate proteins in IL-6-STAT3 signaling pathways; we will also produce gene knockout mice to determine the function of these candidate proteins in inflammation-mediated tumorigenesis in vivo. This project will help to understand the complicated mechanisms of IL-6-STAT3 signaling as well as inflammation-mediated tumorigenesis.

本项目所属集成方向为指南中的“炎-癌转化过程中白细胞介素家族介导的信号通路网络”。已有的研究表明，慢性或非可控性炎症反应是导致肿瘤发生和进展的关键因子。在这个过程中，IL-6-STAT3信号转导调控网络发挥关键作用。在前期工作中，我们利用表达克隆的方法从13000个人和鼠的cDNA克隆中系统筛选了参与IL-6-STAT3信号转导或调控的相关蛋白，获得了119个候选蛋白。本项目将进一步确定这些候选蛋白是否特异性参与IL-6-STAT3信号转导调控；采用生物化学、细胞和分子生物学方法研究这些候选蛋白发挥功能的分子机制；利于基因敲除小鼠模型研究这些候选蛋白在炎-癌转化中的功能。通过该项研究，我们希望阐述IL-6-STAT3信号转导网络的调控机制及其在炎症-癌症转化中的重要作用，为炎症相关的肿瘤治疗鉴定潜在的分子靶标。

本项目所属集成方向为指南中的“炎-癌转化过程中白细胞介素家族介导的信号通路网络”。已有的研究表明，慢性或非可控性炎症反应是导致肿瘤发生和进展的关键因子。在这个过程中，IL-6-STAT3信号转导调控网络发挥关键作用。在我们利用表达克隆的方法从13000个人和鼠的cDNA克隆中系统筛选了参与IL-6-STAT3信号转导或调控的相关蛋白。本项目确定了3个蛋白特异性参与IL-6-STAT3信号转导调控；多个蛋白调控天然免疫和炎症反应。通过该项研究，我们希望阐述IL-6-STAT3信号转导网络的调控机制及其在炎症-癌症转化中的重要作用，为炎症相关的肿瘤治疗鉴定潜在的分子靶标。