S100A14在上皮间质转化、肿瘤微环境和肿瘤干细胞调节中的作用及机制研究

项目名称： S100A14在上皮间质转化、肿瘤微环境和肿瘤干细胞调节中的作用及机制研究

项目编号： No.81472452

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈洪岩

作者单位： 中国医学科学院肿瘤医院

项目金额： 85万元

中文摘要： S100A14是EF手相钙结合蛋白家族成员，在多种肿瘤中表达异常，参与肿瘤发生发展多个过程的调节。我们前期研究发现S100A14可影响肿瘤细胞增殖、凋亡、分化、侵袭和迁移等生物学行为。分子机制研究表明S100A14与RAGE相互作用激活MAPK信号通路影响肿瘤细胞增殖和凋亡，并可与HER2相互作用调节HER2信号通路进而调节乳腺癌细胞增殖。S100A14通过影响p53对MMP2的转录调节MMP2的表达及活性，进而影响细胞侵袭。本研究旨在前期研究的基础上，以乳腺癌为模型，系统深入的研究S100A14在上皮间质转化、肿瘤微环境和肿瘤干细胞调节中的作用及潜在的分子机制，进一步从整体水平序贯动态的评价S100A14参与肿瘤发生发展尤其在肿瘤转移的生物学功能及其分子机理。本研究不仅对理解肿瘤形成、发展和转移的分子机制具有重要的理论意义，对恶性肿瘤的诊断和治疗也具有实践意义。

中文关键词： C21_乳腺肿瘤；S100A14；上皮间质转化；肿瘤微环境；肿瘤干细胞

英文摘要： S100A14 is a member of the EF-hand calcium binding proteins. S100A14 expression is altered in multiple cancers. S100A14 has been implicated in multiple stages of tumorigenesis and progression. Our previous studies showed that S100A14 exerts a wide range of functions such as regulation of cell proliferation, apoptosis, cell invasion and motility. Mechanistic investigation demonstrated that S100A14 affects cell proliferation and apoptosis by activating MAPK signaling pathway via the interaction with RAGE. Meanwhile, S100A14 regulates breast cancer cell proliferation by interacting with HER2 and activating HER2 signaling.Furthermore, S100A14 regulates cell invasion by affecting expression and function of matrix metalloproteinase(MMP)-2 via p53 dependent transcriptional regulation. In this study, we will further explore the function and mechanism of S100A14 in Epithelial-Mesenchymal Transition (EMT),Tumor Microenvironment (TME) and Cancer Stem Cells (CSCs) in breast cancer.We will comprehensively evaluate the biological functions and the underlying mechanism of S100A14 invovled in the tumorigenesis and progression, in particular in tumor metastasis. These studies will significantly increase our understanding of the molecular mechanism of tumorigenesis, progression and metastasis, which has translational implications in the development of new therapies and identification of new biomarkers in breast cancer.

英文关键词： breast Cancer;S100A14;Epithelial-Mesenchymal Transition;Tumor Microenvironment;Cancer Stem Cells