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首页> 外文期刊>Genomics >Reexpression of LGI1 in glioma cells results in dysregulation of genes implicated in the canonical axon guidance pathway.
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Reexpression of LGI1 in glioma cells results in dysregulation of genes implicated in the canonical axon guidance pathway.

机译：LGI1在神经胶质瘤细胞中的重新表达导致规范的轴突引导途径中牵涉的基因失调。

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The LGI1 gene suppresses invasion in glioma cells and predisposes to epilepsy. In a gene expression array comparison between parental cells and T98G cell clones forced to express LGI1, we demonstrate that the canonical axon guidance pathway is the most significantly affected. In particular, aspects of axon guidance that involve reorganization of the actin cytoskeleton, which is also involved in cell movement and invasion, were affected. Analysis of actin fiber organization using fluorescence microscopy demonstrated that different T98G cell clones expressing the exogenous LGI1 gene show high levels of stress fibers compared with controls. Since stress fiber formation is associated with loss of cell mobility, we used scratch wound assays to demonstrate that LGI1-expressing clones show a significant reduction in cell mobility. LGI1 reexpression also resulted in loss of the PDGFRA and EGFR proteins, suggesting a rapid turnover of these receptors despite increased mRNA levels for PDGFRA. LGI1 suppression of invasion is associated with loss of ERK/MAPK1 activation. LGI1 is a secreted protein, and when the culture supernatant from cells expressing FLAG- and GFP-tagged proteins were applied to parental T98G cells, ERK/MAPK1 phosphorylation and cell mobility was suppressed, demonstrating that the LGI1 protein acts as a suppressive agent for cell movement in this assay. These observations support a previous suggestion that LGI1 can reduce cellular invasion in in vitro assays and, as a secreted agent, may be developed as a means of treating metastatic cancer. In addition, this observation provides a mechanistic link for LGI1's common role in metastasis and epilepsy development.
机译：LGI1基因抑制神经胶质瘤细胞的侵袭，易患癫痫病。在亲本细胞和被迫表达LGI1的T98G细胞克隆之间的基因表达阵列比较中，我们证明了规范的轴突引导途径受到的影响最大。特别地，涉及涉及肌动蛋白细胞骨架的重组的轴突引导的方面也受到影响，所述肌动蛋白细胞骨架也参与细胞的移动和侵袭。使用荧光显微镜对肌动蛋白纤维组织的分析表明，与对照相比，表达外源LGI1基因的不同T98G细胞克隆显示出高水平的应激纤维。由于应力纤维的形成与细胞运动能力的丧失有关，我们使用刮伤试验来证明表达LGI1的克隆显示出细胞运动能力的显着降低。 LGI1的重新表达还导致PDGFRA和EGFR蛋白的丢失，这表明尽管PDGFRA的mRNA水平增加，这些受体的快速转换。 LGI1对侵袭的抑制与ERK / MAPK1激活的丧失相关。 LGI1是一种分泌蛋白，当将表达FLAG和GFP标签蛋白的细胞的培养上清液应用于亲本T98G细胞时，ERK / MAPK1的磷酸化和细胞迁移受到抑制，这表明LGI1蛋白可作为细胞的抑制剂分析中的运动。这些观察结果支持先前的建议，即LGI1可以减少体外测定中的细胞侵袭，并且作为一种分泌剂，可以被开发为治疗转移性癌症的手段。此外，该观察结果为LGI1在转移和癫痫发展中的常见作用提供了机理联系。

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