IMP3调控上皮间质转化和肿瘤干细胞进而参与结肠癌发生和转移的机制研究

项目名称： IMP3调控上皮间质转化和肿瘤干细胞进而参与结肠癌发生和转移的机制研究

项目编号： No.81472222

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： 李大卫

作者单位： 复旦大学

项目金额： 72万元

中文摘要： 上皮间质转化（EMT）在肿瘤侵袭转移过程中发挥重要作用。EMT可促进肿瘤细胞获得肿瘤干细胞（CSC）干性，而CSC具有EMT样特征，两者关系密切，但目前对两者相互作用机制仍不清楚。我们前期发现胰岛素样生长因子II mRNA 结合蛋白3（IMP3）是EMT关键调控分子之一，介导EMT参与结肠癌转移；IMP3可维持结肠癌CSC干性； IMP3可能通过活化Wnt/β-catenin通路参与CSC调控，是潜在的CSC干性调控基因。据此我们提出IMP3可能是结肠癌EMT与CSC信号串话（cross talk）的关键节点之一，通过介导Wnt/β-catenin通路调控结肠癌EMT和CSC的内在转化，进而参与结肠癌发生和转移过程。本课题拟通过体内外实验，初步阐明IMP3介导EMT样结肠癌CSC形成和干性维持，进而参与结肠癌发生和转移的机制，最终为结肠癌提供关键的分子标记和干预靶点。

中文关键词： C08_结；直肠肿瘤；IMP3；上皮间质转化；肿瘤干细胞

英文摘要： The epithelial-mesenchymal transition (EMT) plays a critical role during the process of invasion and metastasis in colon cancer. EMT could promote the acquisition of stem-like properties in cancer cells and cancer stem cell (CSC) has EMT properties, both of which are closely linked. However, the underlying mechanism of the interaction between EMT and CSC still remain unclear. We previously found Insulin-like growth factor-II (IGF-II) mRNA binding protein 3 (IMP3) is critical for EMT mediated metastasis of colon cancer. IMP3 could maintain the stem cell property and serve as a potential stem marker, possibly through the transactivation of Wnt/β-catenin signalling. Here we proposed that IMP3 may serve as a key modulator of signalling cross talk between EMT and CSC, which is responsible for the tumorigenesis and metastasis of colon cancer through the interplay between EMT and CSC. In this study, we aim to elucidate the mechanism of IMP3 involved in colon cancer tumorigenesis and metastasis through transactivation of colon CSC with EMT property, which is helpful to identify critical marker and therapeutic target.

英文关键词： Colorectal Tumors;IMP3;EMT;Cancer Stem Cell