上皮-间质转化（EMT）过程中细胞重编程的机制

项目名称： 上皮-间质转化（EMT）过程中细胞重编程的机制

项目编号： No.91219201

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 尚永丰

作者单位： 天津医科大学

项目金额： 350万元

中文摘要： 肿瘤转移是肿瘤病人最常见的死亡原因。上皮-间质转化（EMT）过程在肿瘤转移的初始阶段是非常重要和必不可少的。 这个步骤的实质可能归因于一个事件：EMT过程使肿瘤细胞重编程之后具备了干细胞样特性。本项目旨在通过高通量的RNAi Library筛选，RNA-Seq及ChIP-Seq等实验方法基于生物信息学的贝叶斯因果分析模型寻找上皮细胞转化为间质细胞的细胞重编程过程中的关键通路与关键调控因子，以及其启动与维持EMT的分子机制，特别是表观遗传学机制。目前我们已建立了可靠、量化并可实现高通量筛选的对EMT诱导响应的细胞模型，并且在预实验小规模的RNAi筛选获得了成功。通过本项目的实施，阐明EMT过程中细胞重编程的分子机制，建立和完善EMT的表观遗传学研究的新的技术体系，并为恶性肿瘤的转移预警、诊断、治疗和药物筛选提供新思路、新途径和新靶标。

中文关键词： 乳腺癌；上皮间质转化；表观遗传调控；；

英文摘要： The epithelial-to-mesenchymal transition (EMT) affects critical steps of morphogenesis and tumor metastasis by interconverting epithelial cell type into cells with mesenchymal attributes. EMT programs activated in carcinoma cell enable those cells to acquire cellular traits associated with high-grade malignancy. Moreover, certain epithelial cells that pass through an EMT reprogramming process acquire the self-renewing trait associated with cancer stem cells (CSCs). However, the reprogramming mechanisms of EMT are still poorly understood. In this study, we will search for the essential pathways and key regulators involved in EMT program by using unbiased, genome-wide high throughput approaches including RNAi Library screening, RNA-Sequencing and ChIP-Sequencing techniques, answering questions about overall patterns of reprogramming process of EMT. In our preliminary work, we have constructed a reliable and efficient model cell line which is sensitive to EMT inducers such as TGFb1 and also suitable for high throughput screening strategies. This research will not only elucidate the reprogramming mechanisms that drive and maintain EMT, but also yield promising therapeutic targets and strategies for the prevention of metastasis — the most common fatal consequence of tumorigenesis.

英文关键词： breast cancer；EMT；epigenetic regulation；；