ECM stiffness regulates glial migration in Drosophila and mammalian glioma models
ECM stiffness regulates glial migration in Drosophila and mammalian glioma models
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DOI：
10.1242/dev.106039
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发表时间：
2014-08-01
期刊：
影响因子：
4.6
通讯作者：
Klaembt, Christian
中科院分区：
文献类型：
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作者：
Kim, Su Na;Jeibmann, Astrid;Klaembt, Christian
细胞迁移是胶质细胞的重要特征。在这里，我们使用果蝇眼盘来破译控制神经胶质迁移的分子网络。我们通过激活全胶质细胞PDGF受体（PVR）刺激胶质细胞运动，并鉴定了PVR下游的几个基因。果蝇lox基因是一种非必需基因，编码一种分泌蛋白，可使细胞外基质（ECM）变硬。神经胶质特异性敲低整联蛋白导致ECM软化。此外，我们表明，脂氧合酶的表达调节整合素信号，反之亦然，这表明一个正反馈回路，确保刚性ECM迁移细胞附近。在哺乳动物神经胶质瘤模型中测试了该模型的一般含义，其中Lox特异性抑制剂揭示了ECM刚性在神经胶质瘤细胞迁移中的明显影响。
Cell migration is an important feature of glial cells. Here, we used the Drosophila eye disc to decipher the molecular network controlling glial migration. We stimulated glial motility by pan-glial PDGF receptor (PVR) activation and identified several genes acting downstream of PVR. Drosophila lox is a non-essential gene encoding a secreted protein that stiffens the extracellular matrix (ECM). Glial-specific knockdown of Integrin results in ECM softening. Moreover, we show that lox expression is regulated by Integrin signaling and vice versa, suggesting that a positive-feedback loop ensures a rigid ECM in the vicinity of migrating cells. The general implication of this model was tested in a mammalian glioma model, where a Lox-specific inhibitor unraveled a clear impact of ECM rigidity in glioma cell migration.