The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility
The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility
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DOI：
10.1038/onc.2010.516
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发表时间：
2011-03-01
期刊：
影响因子：
8
通讯作者：
O'Neill, G. M.
中科院分区：
文献类型：
--
作者：
Lees, J. G.;Bach, C. T. T.;O'Neill, G. M.
细胞迁移是转移性疾病的组成部分。细胞在间充质和变形虫迁移模式之间转换的能力使设计成靶向细胞迁移作为抑制转移的手段的成功疗法的开发复杂化。因此，研究调节细胞迁移和使细胞静止的机制是必要的。原肌球蛋白是肌动蛋白相关蛋白，调节肌动蛋白丝动力学的几种效应物的活性。以前，我们已经表明，原肌球蛋白异构体Tm 5 NM 1稳定肌动蛋白丝，抑制细胞迁移的二维培养系统。在这里，我们表明，Tm 5 NM 1抑制多种细胞系的间充质迁移的亚型特异性的方式。Tm 5 NM 1刺激Src激酶活性的下调和三维胶原凝胶中的圆形或椭圆形形态，并且细胞形成伪足的能力显著降低。重要的是，我们发现Tm 5 NM 1抑制间充质向变形样细胞和变形样细胞向间充质的转化。总的来说，我们的数据表明，模仿Tm 5 NM 1过表达的作用代表了一种有效抑制间充质迁移模式的方法。Oncogene（2011）30，1241-1251; doi：10.1038/onc.2010.516; 2010年11月15日在线发表
Cell migration is an integral component of metastatic disease. The ability of cells to transit between mesenchymal and amoeboid modes of migration has complicated the development of successful therapies designed to target cell migration as a means of inhibiting metastasis. Therefore, investigations of the mechanisms that regulate cell migration and render cells stationary are necessary. Tropomyosins are actin-associating proteins that regulate the activity of several effectors of actin filament dynamics. Previously, we have shown that the tropomyosin isoform Tm5NM1 stabilizes actin filaments and inhibits cell migration in a two-dimensional culture system. Here, we show that Tm5NM1 inhibits the mesenchymal migration of multiple cell lines in an isoform-specific manner. Tm5NM1 stimulates the downregulation of Src kinase activity and a rounded or elliptical morphology in three-dimensional collagen gels, and cells have dramatically reduced capacity to form pseudopodia. Importantly, we find that Tm5NM1 inhibits both the mesenchymal to amoeboid and amoeboid to mesenchymal transitions. Collectively, our data suggest that mimicking the action of Tm5NM1 overexpression represents an approach for effectively inhibiting the mesenchymal mode of migration. Oncogene (2011) 30, 1241-1251; doi:10.1038/onc.2010.516; published online 15 November 2010