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首页> 外文期刊>Cell motility and the cytoskeleton >The motility of glioblastoma tumour cells is modulated by intracellular cofilin expression in a concentration-dependent manner.
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The motility of glioblastoma tumour cells is modulated by intracellular cofilin expression in a concentration-dependent manner.

机译:胶质母细胞瘤肿瘤细胞的运动性以浓度依赖的方式受到细胞内cofilin表达的调节。

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The invasive behaviour of tumour cells has been attributed in part to dysregulated cell motility. Members of the ADF/Cofilin family of actin-binding proteins are known to increase microfilament dynamics by increasing the rate at which actin monomers leave the pointed end of the filament and by a filament-severing activity. As depolymerisation is a rate-limiting step in actin dynamics, ADF/Cofilins are suspected to facilitate the motility of cells. To test this, we investigated the influence of cofilin on tumour motility by transient and stably overexpressing cofilin in the human glioblastoma cell line, U373 MG. Several different methods were used to ascertain the level of cofilin in overexpressing clones and this was correlated with their rate of random locomotion. A biphasic relationship between cofilin level and locomotory rate was found. Clones that displayed a moderate amount of overproduction of cofilin were found to have increased rates of locomotion approximately linear to the overproduction of cofilin up to an optimal cofilin level of about 4.5 times that of wild type cells at which the cells were almost twice as fast. However, clones producing more than this optimal amount were found to locomote at progressively reduced speeds. Cells that overexpress cofilin have reduced stress fibres compared to control cells showing that the excess cofilin affects the actin cytoskeleton. We conclude that overexpression of cofilin enhances the motility of glioblastoma tumour cells in a concentration-dependent fashion, which is likely to contribute to their invasiveness. Cell Motil. Cytoskeleton 60:153-165, 2005. (c) 2005 Wiley-Liss, Inc.
机译:肿瘤细胞的侵袭行为部分归因于细胞运动失调。已知肌动蛋白结合蛋白的ADF / Cofilin家族的成员通过增加肌动蛋白单体离开细丝尖端的速率和细丝切断活性来增加微丝动力学。由于解聚是肌动蛋白动力学中的限速步骤,因此怀疑ADF / Cofilins可促进细胞运动。为了测试这一点,我们通过人胶质母细胞瘤细胞系U373 MG中瞬时稳定地过表达cofilin来研究cofilin对肿瘤运动的影响。几种不同的方法被用来确定过表达克隆中cofilin的水平,这与其随机运动的速率有关。发现cofilin水平和运动率之间存在两相关系。发现表现出适度过量生产cofilin的克隆的运动速率与cofilin的过量生产大致成线性关系,直至最佳cofilin水平约为野生型细胞(其细胞几乎快两倍)的最佳4.5倍。然而,发现产生超过该最佳量的克隆以逐渐降低的速度运动。与对照细胞相比,过表达cofilin的细胞的应力纤维减少,这表明过量的cofilin影响肌动蛋白的细胞骨架。我们得出的结论是,cofilin的过度表达以浓度依赖的方式增强了胶质母细胞瘤肿瘤细胞的运动能力,这可能有助于它们的侵袭性。细胞动力。 Cytoskeleton 60:153-165,2005.(c)2005 Wiley-Liss,Inc.

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