TGF-β-MSP58/STRA13信号通路参与调控结肠癌细胞转移的分子机制研究

MSP58 can participate in transcriptional regulation, mitosis of RNA transportand. In fibroblast cells, MSP58 was found that its overexpression can cause malignant transformation and proliferation of fibroblast cells. In our previous data, we have found that MSP58,as an oncogene, was raleted with prolifera tion of colorectal cancer and glioma cell,and the strength of MSP58 expression and 5-year survival of colon cancer is closely related.In molecular lever, MSP58/STAR13 molecules containing the bHLH-like domain synergies involved in tumor cell transcriptional regulation of manyimportant activities of life. Based on these clues, we assume that whether MSP58 be as an intermediate key molecules involved in tumor cell metastasis mediated by TGF-beta-STAR13 signal pathway. This study, we intend to focus on the TGF-β-MSP58/STRA13 signaling pathway for the study of the main line, try to study the pathways involved in the regulation of colon cancer cell metastasis, and provide a theoretical basis for the comprehensive analysis MSP58 oncogene characteristics.

MSP58参与基因转录调控，有丝分裂，RNA运输等。在成纤维细胞中已被证实其表达可引起细胞的恶性转化与增殖。我们前期研究揭示MSP58在结肠癌及脑胶质瘤细胞增殖过程中具有癌基因特性，且MSP58的表达强度与结肠癌5年生存率密切相关。同时在分子水平研究发现MSP58与含有bHLH样结构域的STRA13分子协同作用，参与结肠癌细胞增殖的转录调控。STRA13分子的显性负性突变可阻止体内由TGF-β介导的癌细胞的转移。那么MSP58是否可作为中间关键分子，参与TGF-β-STRA13信号通路所介导的结肠癌细胞转移呢？本课题在前期工作的基础上拟通过TGF-β-MSP58/STRA13信号通路为研究主线，阐明该信号通路参与结肠癌细胞转移的分子机制，为深入解析MSP58的癌基因特性提供理论依据。

我们前期研究揭示MSP58在结肠癌及脑胶质瘤细胞增殖过程中具有癌基因特性，且MSP58的表达强度与结肠癌5年生存率密切相关。本研究通过大样本分析发现MSP58和结肠癌的转移密切相关，是结肠癌转移中的关键分子，同时在分子水平研究发现MSP58与含有bHLH样结构域的STRA13分子协同作用，参与结肠癌细胞增殖的转录调控。STRA13分子的显性负性突变可阻止体内由TGF-β介导的癌细胞的转移。我们通过基因沉默的方法证实，MSP58可作为中间关键分子，参与TGF-β-STRA13信号通路所介导的结肠癌细胞转移。本课题在大样本检测和信号通路方面基本证实结肠癌通过TGF-β-MSP58/STRA13信号通路介导结肠癌细胞的转移，进一步验证了MSP58的癌基因特性。