Angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics.

Angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics.
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血管生成素通过调节应力纤维组装和局部粘附动力学来增强细胞迁移

DOI:
10.1371/journal.pone.0028797
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Xu Z
Xu Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wei S;Gao X;Du J;Su J;Xu Z

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血管生成素(Angiogenin,ANG)作用于血管内皮细胞和癌细胞,但其作用机制尚不清楚。在这项研究中,我们在HeLa细胞中进行了免疫共沉淀试验,并鉴定了14种潜在的ANG相互作用蛋白。在这些蛋白中,β-肌动蛋白、α-肌动蛋白4和非肌肉肌球蛋白重链9是应力纤维组分,并参与细胞骨架的组织和运动,这促使我们研究ANG在细胞迁移中的作用机制。进一步的研究表明,ANG与β-actin和α-actinin 4共定位于迁移细胞的前缘。ANG下调导致应力纤维减少但变粗,动力学降低,这与局灶性粘连扩大有关。ANG缺陷细胞的粘着斑激酶活性和细胞迁移能力显著降低。总之,我们的数据表明,ANG在细胞质中的存在优化了应力纤维组装和粘着斑形成,以适应细胞迁移。ANG促进癌细胞迁移的发现可能为肿瘤转移研究提供新的线索。
Angiogenin (ANG) acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, β-actin, α-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with β-actin and α-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research.
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