项目名称: ABI1拼接异构体在结直肠癌细胞侵袭和转移中的作用机制研究
项目编号: No.81672853
项目类型: 面上项目
立项/批准年度: 2017
项目学科: 医药、卫生
项目作者: 郁卫东
作者单位: 北京大学
项目金额: 25万元
中文摘要: Abl相互作用蛋白1(ABI1)的表达和磷酸化异常涉及结直肠癌细胞的侵袭和转移,影响结直肠癌的预后,但是ABI1拼接异构体(SIs)在其中的作用却并不清楚。结合ABI1-SIs在结直 肠癌细胞中表达的多样性及其分子结构特征,我们推测其对于结直肠癌细胞的侵袭和转移具有重要的调控作用,为此本研究拟1)在系统分析表达谱的基础上,筛选出参与结直肠癌细胞侵袭和转移的关键ABI1-SIs;2)在构建关键ABI1-SIs敲低(或敲除)和/或过表达细胞模型的基础上,从2D体外培养和动物模型水平分析其在结直肠癌细胞侵袭和转移中的作用;3)通过分析可与关键ABI1-SIs发生相互作用的核心分子及其上、下游信号通路,明确其在结直肠 癌细胞侵袭和转移中的作用机制。
中文关键词: C08_结;直肠肿瘤;Abl相互作用蛋白1;拼接异构体;侵袭;转移
英文摘要: Abnormal expression and/or phosphorylation of Abl interactor 1 (ABI1) are associated with colorectal cancer cell invasion and metastasis and function as a potential predicts of prognosis, but ABI1 splice isoforms (ABI1-SIs) for which the functional role is not characterized yet. Taken the specific expression profiles of ABI1-SIs in colorectal cancer with the molecular structure of ABI1-SIs, we supposes that ABI1-SIs might represent an alternative unknown molecular mechanism by which regulating the colorectal cancer cell invasion and metastasis. In this study, 1) we would firstly identify the key ABI1-SIs involved in colorectal cancer cell invasion and metastasis; 2) after construction of ABI1-SIs specific knockdown/knockout and or overexpression cell models, the changes of tumor cellular behavior (including pseudopodium formation, adhesion, migration and invasion) would be analyzed to determine the role of the key ABI1-SIs in colorectal cancer cell migration and invasion, in Vitro 2D and in Vivo; 3) systemic analysis of the upstream and downstream signal pathway would be used to explore the underlying mechanism of key ABI1-SIs in colorectal cancer cell invasion and metastasis.
英文关键词: Colorectal cancer;Abl interactor 1;Splice Isoform;Invasion;Metastasis