p62/SQSTM1 在乳腺癌侵袭、转移中的作用及机制

项目名称： p62/SQSTM1 在乳腺癌侵袭、转移中的作用及机制

项目编号： No.81202105

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： 吕琪

作者单位： 中国人民武装警察部队后勤学院

项目金额： 24万元

中文摘要： 乳腺癌发病率占女性肿瘤发病率首位，复发或转移是乳腺癌致死的主要原因。p62/SQSTM1 (sequestosome 1) 是一个具有多种功能结构域的接头蛋白分子，通过不同的结构域与其他蛋白分子相互作用来传递信号，近年研究表明其还可介导泛素化蛋白的降解。文献报道与本研究前期工作均提示p62在肿瘤恶性进展中发挥着重要作用，但目前尚没有直接的证据表明p62可以促进肿瘤的侵袭、转移。本研究拟以乳腺癌作为研究对象，通过建立稳定表达p62的MCF-7细胞株及稳定干扰p62的MDA-MB-231细胞株，体内、外实验研究p62在乳腺癌侵袭、转移中的作用，并对其相关机制进行研究。为下一步开发以p62作为靶点的抗肿瘤药物提供理论依据。

中文关键词： 自噬；p62；DEDD；肿瘤发生；肿瘤转移

英文摘要： Breast cancer is the leading type of cancer among women today. Metastasis is the spread of tumor to other parts of the body and primarily responsible for breast cancer deaths. p62/SQSTM1 (sequestosome 1) with multiple functional domains, reveals a rich potential for interacting partners consistent with its role as a focal point in signal transduction. p62 also transports polyubiquitinated proteins to degradation by proteasome and autophagy systems. Both our previous works and recent reports demonstrate that p62 plays an important role in the tumor progress. However, there is no direct evidence connecting the p62 with invasion and metastasis in tumor aggressive progress by now. In this study, we will stable express p62 in non metastatic breast cancer cell line MCF-7, and stable knockdown p62 in metastatic breast cancer cell line MDA-MB-231, then verify the function of p62 on invasion and metastasis by in vivo and in vitro comparetive experiments. Furthermore, the potential mechanism of p62 regulating the metastasis will be explored. Our research will provide a direct evidence of taking p62 as a potential therapeutic target for the prevention and treatment of cancer metastasis.

英文关键词： autophagy；p62；DEDD；tumorigenesis；metastasis