干细胞转录因子Oct4/Nanog激活Stat3信号促进肝癌侵袭转移的分子机制

项目名称： 干细胞转录因子Oct4/Nanog激活Stat3信号促进肝癌侵袭转移的分子机制

项目编号： No.81201901

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 殷欣

作者单位： 复旦大学

项目金额： 23万元

中文摘要： Oct4及Nanog是在胚胎干细胞及成体干细胞中表达并维持干细胞自我更新及多能性的关键转录因子。近来研究表明，Oct4及Nanog在多种实体瘤的肿瘤干细胞中阳性表达，并与肿瘤的恶性生物学行为及不良预后相关。申请人前期研究发现：Oct4及Nanog基因在高转移潜能肝癌细胞株上调表达，其阳性表达与肝癌患者根治性切除术后肿瘤复发，转移及不良预后相关。进一步研究提示,Oct4和Nanog可能通过介导Stat3信号活化促进肝癌的侵袭转移，然而其涉及的分子机制及信号通路并不明确。本研究拟通过慢病毒转染技术，建立过表达Oct4及Nanog肝癌细胞株，在体内及体外观察Oct4及Nanog过表达对肝癌恶性生物学行为的影响及其对Stat3及相关下游基因MMPs,VEGF,bFGF,Snail,Slug,Twist等调控作用，明确其促进肝癌侵袭转移的分子机制，为肝癌复发转移的预测及靶向治疗提供新的分子标记物。

中文关键词： Oct4；Nanog；Stat3/Snail 信号通路；上皮间质转化；侵袭转移

英文摘要： Oct4 and Nanog,expressed in both embryonic and adult stem cells,are master transcription factors essential for maintaining stem cells self-renewal and pluripotency.Recently, increasing evidence showed Oct4 and Nanog were also expressed in cancer stem cells and associated with aggressive tumor behaviors and poor prognosis.In previous study,we found both Oct4 and Nanog were linked to metastatic potential in HCC cell lines,and proved coexpression of Oct4 and Nanog can predict recurrence/metastasis and poor clinical outcomes for patients with HCC after curative liver resection.Moreover,results from preliminary experiment suggested Oct4/Nanog may promote invasion and metastasis of HCC through the activation of Stat3 signaling pathway.This study is a further investigation of the possible underlying molecular mechanism of stemness factors Oct4 and Nanog in promoting recurrence/metastasis of HCC. To this end,we will forcibly overexpress Oct4 and Nanog into MHCC97L cell by using plasmid transfection.The role of Oct4 and Nanog in malignant biological behaviors of HCC will be obversed. Phosphorylation of Stat3 and the activation of downstream genes such as MMPs,VEGF,bFGF,Snail,Slug, Twist will also be detected, by a series of in vitro and vivo assays.This is a piloted study involved in stemness factors Oct4 and Nanog

英文关键词： Oct4；Naong；Stat3/Snail pathway；epithelial-mesenchymal transition；invasion and metastasis