转录因子TEAD4在三阴性乳腺癌中的功能和机制研究

项目名称： 转录因子TEAD4在三阴性乳腺癌中的功能和机制研究

项目编号： No.81460401

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王春艳

作者单位： 昆明医科大学

项目金额： 47万元

中文摘要： 乳腺癌是严重危害女性身心健康的最常见的恶性肿瘤，其中三阴性乳腺癌患者的预后最差，目前还没有有效的靶向治疗手段。Hippo信号通路已成为癌症诊治靶标的研究热点，TEADs是Hippo信号通路中重要的转录因子,我们前期研究发现TEAD4在三阴性乳腺癌中高表达，TEAD4可以促进三阴性乳腺癌细胞增殖、生存和迁移，TEAD4能够和KLF5相互作用下调细胞周期抑制蛋白p27的表达。本项目将进一步深入研究TEAD4促进乳腺癌细胞的增殖、生存、转移的功能和分子机制，并在小鼠体内明确TEAD4在乳腺癌中的作用，明确其是否作为一个新的三阴性乳腺癌靶向治疗标志物和治疗靶点。

中文关键词： 乳腺癌；转录因子；TEAD4

英文摘要： Breast cancer is one of the most common malignancies which continue to be a serious health problem in women. Of particular concern is triple negative breast cancer (TNBC) which does not respond well to standard therapy and is associated with poor overall patient prognosis. Hippo signaling pathway plays important role in cancer development and provides targets for cancer diagnosis and treatment. TEADs are key transcription factors mediating the functions of the Hippo pathway. Preliminary data suggest that TEAD4 is over-expressed in breast tumors including TNBC,promotes breast cancer cell proliferation ，survival and metastasis. interacts with KLF5 and suppresses the expression of p27. In the current study, first, we will further study the functional mechanisms of TEAD4 in promoting breast cancer cell proliferation, survival, and metastasis; second, we will clarify whether TEAD4 functions as a novel transcription factor for p27; and finally, we will investigate the role of TEAD4 in breast cancer tumorigenesis in mice and provide evidence for developing TEAD4 as a new prognosis biomarker and therapeutic target for TNBC treatment.

英文关键词： breast cancer;transcriptional factor;TEAD4