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丝氨酸蛋白酶抑制剂(SERPIN)B1抑制胶质瘤细胞的迁移和侵袭。

Serine protease inhibitor (SERPIN) B1 suppresses cell migration and invasion in glioma cells.

作者信息

Huasong Gao, Zongmei Ding, Jianfeng Huang, Xiaojun Qiu, Jun Guo, Sun Guan, Donglin Wang, Jianhong Zhu

机构信息

Department of Neurosurgery, Fudan University Huashan Hospital, National Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200000, China.

Department of Pathology, Subei People's Hospital, Yangzhou 225001, Jiangsu, China.

出版信息

Brain Res. 2015 Mar 10;1600:59-69. doi: 10.1016/j.brainres.2014.06.017. Epub 2014 Jun 23.

Abstract

The serine protease inhibitor (SERPIN) B1 is expressed in numerous human tumors, but little is known regarding its role in the pathophysiology of glioma. In this paper, we report that SERPINB1 expression was down-regulated in high-grade human glioma tissue samples and glioblastoma cell lines. To investigate the role of SERPINB1 in glioma migration and invasion, we generated human glioma cell lines in which SERPINB1 was either overexpressed or depleted. Overexpression of SERPINB1 suppressed, while elimination of SERPINB1 promoted, the migration and invasion of glioma cells. SERPINB1 inhibited glioma migration and invasion probably by dampening the expression of matrix metalloproteinase-2 (MMP-2). Molecular data showed that the effect of SERPINB1 in glioma cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) involved in the downregulation of the expressions of MMP-2. In a multivariate analysis, high SERPINB1 expression was showed to be associated with good prognosis in glioma. In conclusion, our data suggest that SERPINB1 negatively regulates glioma cell migration and invasion probably by abrogating the expression of MMP-2 and the activation of FAK. We suggest that SERPINB1 may offer the application in clinical medicine.

摘要

丝氨酸蛋白酶抑制剂(SERPIN)B1在多种人类肿瘤中均有表达,但关于其在胶质瘤病理生理学中的作用却知之甚少。在本文中,我们报告称SERPINB1在高级别人类胶质瘤组织样本和胶质母细胞瘤细胞系中的表达下调。为了研究SERPINB1在胶质瘤迁移和侵袭中的作用,我们构建了SERPINB1过表达或缺失的人类胶质瘤细胞系。SERPINB1的过表达抑制了胶质瘤细胞的迁移和侵袭,而SERPINB1的缺失则促进了其迁移和侵袭。SERPINB1可能通过抑制基质金属蛋白酶-2(MMP-2)的表达来抑制胶质瘤的迁移和侵袭。分子数据表明,SERPINB1在胶质瘤细胞中的作用可能是通过持续使参与MMP-2表达下调的粘着斑激酶(FAK)磷酸化失活来介导的。多变量分析显示,SERPINB1高表达与胶质瘤的良好预后相关。总之,我们的数据表明,SERPINB1可能通过消除MMP-2的表达和FAK的激活来负向调节胶质瘤细胞的迁移和侵袭。我们认为SERPINB1可能在临床医学中具有应用价值。

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