The FASEB J：flightless分子或抑制癌细胞转移

近日，刊登在国际杂志FASEB Journal上的一篇研究报告指出，一种名为“flightless”的分子可以明显帮助有效控制癌细胞在不同组织间转移的速度。正是由于flightless分子的存在，癌症转移的速度被有效的遏制了。Flightless分子可以增加细胞之间的粘稠度，包括癌症细胞，这样可以明显减缓癌细胞扩散的速度。

研究flightless以及其控制细胞运动的速度为未来控制癌症的发展提供了新的思路，研究者Christopher表示，我们希望有一天调节细胞运动的疗法可以被用来控制癌细胞扩散速度。

文章中，研究者使用了三组细胞，一组细胞可以产生正常的flightless分子，一组细胞不能产生，一组细胞可以高表达该分子。随后研究者研究了这些组细胞的运动比率，并且检测了这些细胞的特殊部分是否可以使细胞本身粘附于组织上面，结果显示，flightless分子在细胞运动迁移的速度上存在显著性的效应。

在一个器官中对付单一的肿瘤是非常困难的，但是许多癌症的转移为治疗增加了新的障碍，因此这项研究成果揭示了flightless分子对于阻止癌症细胞迁移或者转移速度，进而抑制癌症转移，这无疑是癌症病人治疗的一大希望。

编译自：'Flightless' Molecule May Prevent Cancer from Spreading from One Tissue to Another

doi:10.1096/fj.11-202051
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Flightless I is a focal adhesion-associated actin-capping protein that regulates cell migration

Ibrahim Mohammad*, Pamma D. Arora*, Yeganeh Naghibzadeh*, Yongqiang Wang*, Jeff Li*, Wendall Mascarenhas*, Paul A. Janmey†, John F. Dawson‡ and Christopher A. McCulloch*,1

The role of adhesion-associated actin-binding proteins in cell migration is not well defined. In mouse fibroblasts we screened for focal adhesion-associated proteins that were isolated with collagen-coated beads and detected by tandem mass spectrometry. We identified flightless I (FliI) as an actin-binding protein in focal adhesion fractions, which was verified by immunoblotting. By confocal microscopy most FliI was distributed throughout the cytosol and in focal adhesions. By sedimentation assays and in vitro binding assays, we found that FliI associates with actin filaments and actin monomers. Assays using purified proteins showed that FliI inhibits actin polymerization and caps but does not sever actin filaments. Cells with FliI knockdown or cells overexpressing FliI migrated more or less rapidly, respectively, than wild-type controls. Compared with controls, cells with FliI knockdown were less adherent than wild-type cells, exhibited reduced numbers of focal adhesions containing activated β1 integrins and vinculin, and exhibited increased incorporation of actin monomers into nascent filaments at focal adhesions. These data indicate that FliI regulates cell migration through its localization to focal adhesions and its ability to cap actin filaments, which collectively affect focal adhesion maturation.—Mohammad, I., Arora, P. D., Naghibzadeh, Y., Wang, Y., Li, J., Mascarenhas, W., Janmey, P. A., Dawson, J. F., McCulloch, C. A. Flightless I is a focal adhesion-associated actin-capping protein that regulates cell migration.