14-3-3ζ-Hsp27复合物促进非小细胞肺癌上皮间皮转化及机制的研究

项目名称： 14-3-3ζ-Hsp27复合物促进非小细胞肺癌上皮间皮转化及机制的研究

项目编号： No.81201834

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： 丁建勇

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 近年，上皮间皮转化(EMT)在肿瘤侵袭转移中的作用(包括肺癌)颇受关注。14-3-3ζ是一种可溶性酸性蛋白质，其参与多种信号转导。新近研究示其在肿瘤中过表达并与患者预后负相关；且证实其过表达在TGFβ诱导细胞EMT过程中起关键作用，其被视为一潜在的癌基因。我们前期研究发现：1高分期肺癌中14-3-3ζ表达明显高于低分期肺癌且与患者预后负相关，下调其表达可抑制细胞侵袭；2其高表达可诱导ERK1/2激活，免疫共沉淀结合质谱分析证实其与Hsp27等多种蛋白形成复合物；3在肺癌细胞中下调Hsp27表达可逆转14-3-3ζ诱导的细胞表型,如EMT。考虑到Hsp27在肿瘤中的重要作用及其功能与14-3-3ζ高度重叠,本研究拟：在肺癌组织中研究14-3-3ζ与Hsp27表达，分析两者的相关性及与患者预后关系；在细胞中研究两者表达有无相互影响及与肺癌EMT的关系；最后分子水平研究其具体机制并体内实验证实。

中文关键词： 非小细胞肺癌；14-3-3Zeta；热休克蛋白27；侵袭与转移；上皮-间质转化

英文摘要： In recent years, epithelial mesothelioma transitions (EMT) in tumor invasion and metastasis (including lung cancer) is of great concern. 14-3-3ζ is a soluble acidic protein, and it participate in a variety of signal transduction. Recent studies have shown that it is overexpressed in many tumor tissues and associated with the poor patient's prognosis. Its overexpression has been reported to be involved in the TGFβ-induced EMT of tumor cells; and it has been viewed as a potential oncogene. Our previous study found that: 1 14-3-3ζ expression in high-stage lung cancer was significantly higher than those of the low-stage lung caner and negatively correlated with the prognosis of patients, and its reduced expression inhibited tumor cells invasion; 2 its overexpression can up-regulate the activation of ERK1/2, and Co-immunoprecipitation combined with mass spectrometry analysis confirmed that 14-3-3ζ form a complex with Hsp27 and the other proteins; 3 the reduction in Hsp27 expression in lung cancer cells reversed the 14-3-3ζ-induced phenotype, such as EMT. Taking into account the important role of Hsp27 in tumors and the high overlap of the function between Hsp27 and 14-3-3ζ, here, we try to explore the expression of 14-3-3ζ and Hsp27 in lung cancer and the corresponding adjacent tissues, and analyze their relevance a

英文关键词： Non-small-cell lung carcinoma；14-3-3ζ；Hsp27；Invasion and Metastasis；Epithelial-mesenchymal transitions