A direct interaction between fascin and microtubules contributes to adhesion dynamics and cell migration.
A direct interaction between fascin and microtubules contributes to adhesion dynamics and cell migration.
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DOI：
10.1242/jcs.175760
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发表时间：
2015-12-15
影响因子：
4
通讯作者：
Parsons M
中科院分区：
文献类型：
--
作者：
Villari G;Jayo A;Zanet J;Fitch B;Serrels B;Frame M;Stramer BM;Goult BT;Parsons M
筋膜蛋白是一种肌动蛋白结合和捆绑蛋白，在大多数上皮性癌症中高度上调。法辛在体外促进细胞的迁移和黏附，在体内促进肿瘤细胞的转移。然而，筋膜蛋白潜在的非肌动蛋白结合作用仍不清楚。在这里，我们第一次展示了束蛋白可以直接与微管细胞骨架相互作用，这并不依赖于束蛋白-肌动蛋白捆绑。微管结合有助于对粘着斑动力学和细胞迁移速度的依赖于筋膜蛋白的控制。我们还发现，Fasin与粘着斑激酶(FAK，也称为PTK2)和Src形成一个复合体，该信号通路位于Fasin-微管联系的下游，控制着黏附的稳定性。这些发现阐明了非肌动蛋白依赖的筋膜蛋白的新作用，并可能对转移性疾病中针对筋膜蛋白的治疗方案的设计有一定的指导意义。摘要：筋膜蛋白不依赖于F-肌动蛋白的结合而直接与微管结合，这有助于微管的动力学、黏附组装和细胞迁移。
Fascin is an actin-binding and bundling protein that is highly upregulated in most epithelial cancers. Fascin promotes cell migration and adhesion dynamics in vitro and tumour cell metastasis in vivo. However, potential non-actin bundling roles for fascin remain unknown. Here, we show for the first time that fascin can directly interact with the microtubule cytoskeleton and that this does not depend upon fascin-actin bundling. Microtubule binding contributes to fascin-dependent control of focal adhesion dynamics and cell migration speed. We also show that fascin forms a complex with focal adhesion kinase (FAK, also known as PTK2) and Src, and that this signalling pathway lies downstream of fascin–microtubule association in the control of adhesion stability. These findings shed light on new non actin-dependent roles for fascin and might have implications for the design of therapies to target fascin in metastatic disease. Summary: Fascin associates directly with microtubules independently of F-actin binding, and this contributes to microtubule dynamics, adhesion assembly and cell migration.