具核梭杆菌感染激活IL-6/STAT3通路调控结直肠癌EMT及肿瘤干细胞形成

项目名称： 具核梭杆菌感染激活IL-6/STAT3通路调控结直肠癌EMT及肿瘤干细胞形成

项目编号： No.81502052

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： 岳超

作者单位： 南京医科大学

项目金额： 18万元

中文摘要： 具核梭杆菌(Fn)在结直肠癌(CRC)患者粘膜中大量增加已在多份研究中得到确认。本项目前期发现：Fn的增加与浸润深度及淋巴结转移正相关，提示Fn可能参与了CRC转移过程；将Fn与大肠癌细胞共培养后上皮间质化（EMT）相关蛋白及结肠癌干细胞（CSC）标志物CD44水平升高，且CD44升高主要发生在EMT细胞中，表明Fn感染可能通过EMT样作用产生CSC；基因芯片分析显示IL-6/STAT3通路相关靶基因表达水平升高，说明IL-6/STAT3通路可能在此过程中扮演重要角色。因此，本研究利用前期已从CRC组织中分离培养出的Fn菌株与肠癌细胞共培养，检测EMT、CSC及IL-6/STAT3通路标记物水平变化，旨在阐明: ①CRC时具核梭杆菌可通过EMT样作用产生CSC；②Fn感染可激活IL-6/STAT3信号通路调控EMT及CSC的产生。本项目研究将为结直肠癌的诊断、预防和治疗提供新思路.

中文关键词： 具核梭杆菌；结；直肠肿瘤；上皮间质化；肿瘤干细胞；；IL-6/STAT3信号通路

英文摘要： It has been suggested that bacterial dysbioses have been linked to colorectal cancer (CRC) and Fusobacterium nucleatum (Fn) is more abundant in CRC cases than controls. We also found that compared to normal mucosal biopsies, shifts in microbial composition were detected in tumer mucosal biopsies. A higher presence of Fn and a link between the abundance of Fn and disease progression step and tumor severity were found.Therefore, Fn played an important role in tumor initiation and progression,especially in tumor invasion and metastasis which were associateed with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC). We found increases in EMT markers and CD44 when SW480 cells were co-cultured with Fn. Moreover, EMT-like cells showed a clearly higher expression of CD44. Therefore, it is possible that Fn generates cells with CSC via EMT-like changes. Genes downstream of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) showed a clearly higher expression. It suggested IL-6/STAT3 played an important role in this progress. Hence, Fn stains which were isolated from human mucosal were cultivated and utilized. Markers of EMT, CSC and IL-6/STAT3 signaling pathway will be tested. We want to identify:1) Fn generates cells with CSC via EMT-like changes; 2) Fn regulates EMT-like changes and the formation of cancer stem cells through a novel IL6/Stat3 signaling pathway.This project will contribute to the etiology, diagnosis, treatment, and prevention of CRC.

英文关键词： Fusobacterium nucleatum ;colorectal cancer ;epithelial-mesenchymal transition;cancr stem cell; IL-6/STAT3 signaling pathway