干扰素诱导的跨膜蛋白1在结直肠癌转移中的作用及机制探索

项目名称： 干扰素诱导的跨膜蛋白1在结直肠癌转移中的作用及机制探索

项目编号： No.81201641

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1

项目作者： 喻芳

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 转移性结直肠癌患者预后差，有远处转移的4期患者5年生存率小于10%。确定调控结直肠癌转移的生物标志物是提高结直肠癌患者预后的关键。申请人先前在神经胶质瘤中的研究结果显示，降低干扰素诱导的跨膜蛋白1（IFITM1）的表达可抑制神经胶质瘤细胞的生长及瘤细胞的迁移、侵袭能力。我们的预实验结果显示IFITM1 mRNA的表达在大多数结直肠癌组织中升高，且IFITM1蛋白可调控结直肠癌细胞中肿瘤转移抑制基因Caveolin-1的表达，提示IFITM1蛋白与结直肠癌的发生、转移相关。为此，本课题拟采用大样本结直肠癌组织芯片检测IFITM1蛋白在结直肠癌组织中的表达，分析其与结直肠癌发生、转移、TNM分期等临床指标的相关性；利用体外细胞和体内动物实验验证IFITM1蛋白对结直肠癌转移的促进作用；探索阐明IFITM1蛋白促进结直肠癌转移的可能分子机制。研究结果将有助于确立新的评价结直肠癌预后的生物标志物。

中文关键词： IFITM1；结直肠癌；转移；CAV1；

英文摘要： The patients of invasive colorectal cancer have poor prognosis, and the survival rate of those in stage IV is less than 10%. Establishment of biological markers regulating invasion of colorectal cancer is critical to improve the prognosis. The previous study of applicant in glioma shows that knocking down the expression of interferon induced transmembrane protein 1 (IFITM1) could inhibit the proliferation, migration and invasion of glioma cells. Our preliminary data shows that the mRNA expression of IFITM1 is increased in most colorectal cancer tissues, and the expression of Caveolin-1, a tumor invasion suppressor gene is regulated by IFITM1, suggesting that IFITM1 is related to carcinogenesis and invasion of colorectal cancer. Furthermore, we plan to first detect the expression of IFITM1 in large tissue samples of colorectal cancer by tissue microarray, and analyze the possible relationship of IFITM1 expression with carcinogenesis, invasion and TNM staging of colorectal cancer; secondly, validate the promotion effect of IFITM1 on colorectal cancer invasion in vitro and in vivo; thirdly, explore the possible molecular mechanism of IFITM1 in colorectal cancer invasion. The study results might contribute to set up a novel biological marker for prognosis evaluation of colorectal cancer.

英文关键词： IFITM1；Colorectal cancer；Metastasis；CAV1；