项目名称： SND1与TGFβ通路交互调控对乳腺癌转移影响的研究

项目编号： No.81202102

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： 于林

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 癌细胞转移是乳腺癌患者死亡的首要原因。前期工作发现乳腺癌SND1表达水平与其转移表型密切相关，激活TGFβ通路可上调乳腺癌细胞SND1表达，SND1又可上调TGFβ通路活性。据此我们提出乳腺癌细胞存在SND1/TGFβ通路异常交互性正反馈调控环路并促进乳腺癌转移的研究假说。本项目研究的中心思想是：(1)了解乳腺癌细胞过表达SND1与TGFβ通路过度激活的相互关系，确定乳腺癌细胞是否存在SND1与TGFβ通路的交互性正反馈调控环路；(2)找出在乳腺癌细胞中参与该异常调控环路信号传递过程的关键功能蛋白种类，明确它们的相互作用位点和作用方式，揭示SND1与TGFβ通路彼此上调的分子机制；(3)阐明乳腺癌SND1/TGFβ通路交互调控异常，对乳腺癌细胞转移的作用、作用地位及其作用的确切分子机制。旨在为最终阐明乳腺癌转移的分子机制提供重要线索，为研发乳腺癌转移诊疗新技术提供客观的依据。

中文关键词： 转化生长因子β通路；乳腺癌；肿瘤转移；交互调控；

英文摘要： Metastasis is the leading cause of death in breast cancer patients. The previous work showed that SND1 expression level is related with breast cancer metastatic phenotype, the activation of TGFβ pathway up-regulate SND1 expression in breast cancer cells, SND1 could also up-regulate TGFβ pathway activity. According to these results, we propose the hypothesis that there is a positive feedback loop of SND1/TGFβ crosstalk regulation in breast cancer. The following parts are the central idea of this project: (1)understanding the relationship between SND1 over-expression and TGFβ pathway excessive activation in breast cancer cells, determining whether the SND1/TGFβ pathway positive feedback loop exists in breast cancer cells; (2)finding out the interaction sites and activation domain of the key functional proteins involved in the crosstalk process; (3)revealing the role of SND1/TGFβ pathway crosstalk dis-organization in breast cancer metastasis process. Through the research of this subject, we try to provide additional proof for the molecular mechanisms of breast cancer metastasis, we also hope we could provide more theoretical evidence for developing new technology of the diagnosis and treatment of metastatic breast cancer.

英文关键词： TGFβ signaling pathway；breast cancer；tumor metastasis；regulation interaction；