PPIB蛋白影响结直肠癌细胞凋亡的作用及其分子机制研究

项目名称： PPIB蛋白影响结直肠癌细胞凋亡的作用及其分子机制研究

项目编号： No.81201539

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： 乐飞

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 肽酰脯氨基顺反异构酶B（PPIB）是一种特异性定位于内质网的分子伴侣蛋白，主要负责催化新合成未折叠蛋白的肽酰脯氨键的顺反异构反应。既往对该蛋白的研究主要集中于病毒感染领域，尚未见与恶性肿瘤相关的研究报道。近期，本课题组利用蛋白质组学技术发现结直肠癌组织高表达PPIB蛋白，进而利用RNAi技术抑制PPIB表达后，结肠癌细胞系在裸鼠皮下的成瘤能力显著减弱，同时发生细胞凋亡，提示PPIB蛋白在结直肠癌的发生和发展过程中可能发挥了重要作用。本课题拟在这些发现的基础上，进一步明确PPIB蛋白对细胞凋亡的影响效应，深入研究PPIB蛋白影响结直肠癌细胞凋亡的信号转导通路和分子机制，这对揭示PPIB蛋白的生物学作用、细胞凋亡的分子机制和进一步认识结直肠癌的发病机制等具有重要理论意义。随着研究的深入，PPIB蛋白可望成为治疗结直肠癌的潜在药物靶标，从而为靶向治疗结直肠癌药物的研发提供理论基础。

中文关键词： 肽酰脯氨基顺反异构酶B；结直肠癌；细胞凋亡；肿瘤发生；内质网应激

英文摘要： Peptidyl-propyl isomerase B (PPIB) is a molecular chaperone located in endoplasmic reticulum, which helps the folding of neosynthesized proteins. Previous literatures proved that PPIB plays key roles in the field of viral infections. The relationship between PPIB and cancer has not been investigated yet. Via proteomic techniques, our team recently found that PPIB protein is overexpressed in colorectal cancer tissues compared to those paired controls. Morevoer, when the expression of PPIB was inhibited with RNAi technique, colorectal cancer cells performed weaker tumorigenicity in nude mice. Apoptosis was notebly observed in the paraffin sections of those xenograft tumors. The evidences above indicated that PPIB may play important roles in the processes of tumorigenesis and development of colorectal cancer. Based on our findings, we plan to study the effect of PPIB on the apoptosis of colorectal cancer cells, profile involved signal transduction pathways, and try to elucidate relative molecular mechanisms. This study may help uncover PPIB's novel functions and corresponding apoptotic mechanism, which could bring us a better understanding of colorectal cancer. With more and more evidences, PPIB could serve as a promising therapeutic target, and we could providing further information for the research and develepmen

英文关键词： PPIB；colorectal cancer；apoptosis；tumorigenesis；ER stress