Laboratory of Mechanisms of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
Cell Migration and Invasion and Spatio-Temporal Regulation of Antigen Presentation teams, UMR144/U932 Institut Curie, Paris, France.
Int Rev Cell Mol Biol. 2020;356:197-256. doi: 10.1016/bs.ircmb.2020.06.002. Epub 2020 Jul 16.
During development of metastasis, tumor cells migrate through different tissues and encounter different extracellular matrices. An ability of cells to adapt mechanisms of their migration to these diverse environmental conditions, called migration plasticity, gives tumor cells an advantage over normal cells for long distant dissemination. Different modes of individual cell motility-mesenchymal and amoeboid-are driven by different molecular mechanisms, which largely depend on functions of the actin cytoskeleton that can be modulated in a wide range by cellular signaling mechanisms in response to environmental conditions. Various triggers can switch one motility mode to another, but regulations of these transitions are incompletely understood. However, understanding of the mechanisms driving migration plasticity is instrumental for finding anti-cancer treatment capable to stop cancer metastasis. In this review, we discuss cytoskeletal features, which allow the individually migrating cells to switch between mesenchymal and amoeboid migrating modes, called mesenchymal-to-amoeboid transition (MAT). We briefly describe main characteristics of different cell migration modes, and then discuss the triggering factors that initiate MAT with special attention to cytoskeletal features essential for migration plasticity.
在转移的发展过程中,肿瘤细胞通过不同的组织迁移,并遇到不同的细胞外基质。细胞适应其迁移到这些不同环境条件的机制的能力,称为迁移可塑性,使肿瘤细胞比正常细胞具有更有利的远距离扩散优势。不同的细胞运动模式——间质和阿米巴样——由不同的分子机制驱动,这些机制在很大程度上取决于肌动蛋白细胞骨架的功能,而肌动蛋白细胞骨架的功能可以通过细胞信号机制在很大范围内进行调节,以响应环境条件。各种触发因素可以将一种运动模式切换到另一种运动模式,但这些转换的调节机制尚不完全清楚。然而,对驱动迁移可塑性的机制的理解对于寻找能够阻止癌症转移的抗癌治疗方法是至关重要的。在这篇综述中,我们讨论了允许单个迁移细胞在间质和阿米巴样迁移模式之间切换的细胞骨架特征,称为间质到阿米巴样转变(MAT)。我们简要描述了不同细胞迁移模式的主要特征,然后讨论了引发 MAT 的触发因素,特别关注对迁移可塑性至关重要的细胞骨架特征。