Gab2 expression in glioma and its implications for tumor invasion
Gab2 expression in glioma and its implications for tumor invasion
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Gab2在胶质瘤中的表达及其对肿瘤侵袭的意义
DOI：
10.3109/0284186x.2012.750032
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发表时间：
2013-11-01
期刊：
影响因子：
3.1
通讯作者：
Zhang, Baogang
中科院分区：
文献类型：
--
作者：
Shi, Lihong;Sun, Xiuning;Zhang, Baogang
胶质瘤具有侵袭性高、预后差的特点。更好地了解神经胶质瘤细胞的侵袭机制对于设计有效的疗法至关重要。最近，Grb2 相关结合物 2 (Gab2) 是 DOS/Gab 支架接头家族的成员，据报道在人类癌症的发生和进展中发挥重要作用。然而，Gab2在胶质瘤的迁移和侵袭中是否发挥作用尚不清楚。本研究试图探讨Gab2表达与胶质瘤进展的关系以及Gab2在胶质瘤细胞侵袭中的分子机制。方法。 Western blot检测配对的胶质瘤组织及其正常脑组织中Gab2的表达。采用免疫组织化学方法检测163例经组织学诊断的胶质瘤中Gab2的表达情况。在 SCID 小鼠脑中体外和体内研究了 Gab2 减少的神经胶质瘤细胞和对照神经胶质瘤细胞的侵袭特性。结果。研究发现 Gab2 在神经胶质瘤和一部分癌细胞系中高表达。统计分析表明，Gab2 的上调与胶质瘤的 WHO 分级相关（p < 0.01），并且 Gab2 表达水平高的患者生存时间较短（p < 0.01）。在动物实验中，通过 siRNA 敲低 Gab2 抑制了神经胶质瘤细胞侵入 SCID 小鼠大脑的能力。在细胞研究中，siRNA 减少 Gab2 可通过介导细胞骨架重排和 MMP 表达来抑制神经胶质瘤细胞的迁移和侵袭。此外，IGF-1 诱导的 pAkt 和 pmTOR 磷酸化因 Gab2 的敲低而受到抑制。结论。 Gab2可能是胶质瘤的有用预后标志物和胶质瘤侵袭干预的新治疗靶点。
Gliomas are characterized by high invasiveness and poor prognosis. Better understanding of the mechanism of invasion in glioma cells is essential to the design of effective therapy. Recently Grb2-associated binder 2 (Gab2), a member of the DOS/Gab family of scaffolding adapters, has been reported to play important roles in the development and progression of human cancers. However, it is not known whether Gab2 has any role in the migration and invasion of gliomas. This study attempts to investigate the association between Gab2 expression and progression of gliomas and the molecular mechanism of Gab2 in the glioma cell invasion. Methods. The expression of Gab2 in pairs of matched glioma tissues and their normal brain tissues was detected by Western blot. Immunohistochemistry was applied to evaluate the expression of Gab2 in 163 cases of histologically diagnosed gliomas. The invasive character of Gab2 decreased glioma cells and control glioma cells were investigated in vitro and in vivo in SCID mice brain. Results. Gab2 is found to be high expressed in gliomas and a subset of cancer cell lines. Statistical analysis suggested that the up-regulation of Gab2 correlated with the WHO grade of gliomas (p < 0.01) and that patients with high Gab2 expression levels exhibited shorter survival time (p < 0.01). In an animal experiment, knockdown of Gab2 through siRNA inhibited invasive ability of glioma cells into the brain of SCID mice. In cell research, reduction of Gab2 by siRNA inhibits the migration and invasion of glioma cells by mediating cytoskeleton rearrangement and MMPs expression. Additionally, IGF-1-induced pAkt and pmTOR phosphorylation was suppressed by the knockdown of Gab2. Conclusion. Gab2 may be a useful prognostic marker for gliomas and a novel therapeutic target for glioma invasion intervention.