项目名称: IL-13/IL-13Rα2/11βHSD2特异性信号通路促进结肠癌肝转移的分子机制研究
项目编号: No.81472705
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: 姜立
作者单位: 华中科技大学
项目金额: 72万元
中文摘要: 近年来的研究表明,IL-13/IL-13Rα2促进包括结肠癌在内的多种恶性肿瘤的转移。然而,IL-13Rα2不含有与已知效应蛋白作用的结构域,其激活下游信号通路的分子机制至今仍不清楚。我们前期研究发现IL-13能通过作用于IL-13Rα2特异性上调结肠癌细胞内11βHSD2的表达,并证明11βHSD2能通过COX2和Akt通路促进结肠癌细胞的生长和转移,因此我们推测结肠癌细胞内存在IL-13Rα2/11βHSD2特异性信号通路并在结肠癌的转移中起重要作用。为了阐明该特异性信号通路促进结肠癌肝转移的分子机制,我们拟综合运用分子生物学、蛋白组学、激酶芯片分析、结肠癌肝转移动物模型、生物信息学结合临床等多种技术手段证实11βHSD2是IL-13/IL-13Rα2 促进结肠癌肝转移的重要效应分子并探讨IL-13/IL-13Rα2激活该效应蛋白的具体分子机制。
中文关键词: C08_结;直肠肿瘤;白介素13;白介素13受体α2;11β-羟基类固醇脱氢酶2;肿瘤转移
英文摘要: Recent studies indicate that IL-13,through its receptor IL-13Rα2,promotes the metastasis of cancer cells from different cancer types including colon cancer.The mechanism through which IL-13Rα2 activates its downstream signaling pathway remains unclear as IL-13Rα2 has no known protein binding domain. Our previous studies demonstrated the IL-13Rα2-dependent induction of 11βHSD2 expression in colon cancer cells,and the important role of 11βHSD2 in promoting tumor cell metastasis through activating PI3K/Akt pathway and upregulation of COX2. Therefore,we hypothesize that IL-13/IL-13Rα2/11βHSD2 might be a colon cancer cell specific pathway which is crucial to colon cancer metastasis.In current study, by using multiple methods involving molecularbiology,proteomics,kinase array,animal model and clinical analysis,we will determine the significance of 11βHSD2 in mediating the promotion of colon cancer metastasis by IL-13/IL-13Rα2 and investigate the potential mechanism through which IL-13/IL-13Rα2 activate their downstream pathway in colon cancer cells.
英文关键词: ;IL-13;IL-13Rα2;11βHSD2;tumor metastasis