IFOM, The FIRC Institute of Molecular Oncology, via Adamello 16, 20139 Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, via Adamello 16, 20139 Milan, Italy.
IFOM, The FIRC Institute of Molecular Oncology, via Adamello 16, 20139 Milan, Italy; University of Milan, School of Medicine, Department of Oncology and Hemato-Oncology-DIPO, Milan, Italy.
Curr Opin Cell Biol. 2018 Oct;54:9-17. doi: 10.1016/j.ceb.2018.02.006. Epub 2018 Mar 12.
An explosive growth in knowledge, in the last two decades, has conferred a new dimension to the process of endocytosis. Endocytic circuitries have come into focus as a pervasive system that controls virtual all aspects of cell biology. A few years ago, we proposed the term 'endocytic matrix' to define a cellular network of signalling wiring that is at the core of the cellular blueprint. A primary role of the endocytic matrix is the delivery of space-resolved and time-resolved signals to the cell in an interpretable format, and, as such, it has profound consequences on polarized cellular and supra-cellular functions, first and foremost, cell motility. Here, we describe a set of recent results that expand this notion and illuminate how endocytic matrix dynamically controls the plasticity of migratory strategies. We further highlight the impact of inter-organelle contact sites on motility and the role of organelle positioning in this process. Finally, we illustrate how global perturbation of the endocytic circuitry influences cellular and supra-cellular mechanics, ultimately controlling a solid-to-liquid-like transition in the mode of motility with potential consequences on cancer dissemination.
在过去的二十年中,知识呈爆炸式增长,为胞吞作用的过程赋予了新的维度。作为一种普遍存在的系统,胞吞循环控制着细胞生物学的几乎所有方面,这一系统已成为焦点。几年前,我们提出了“胞吞基质”一词,用以定义细胞信号网络,该网络是细胞蓝图的核心。胞吞基质的主要作用是以可解释的格式向细胞传递空间分辨和时间分辨信号,因此,它对极化细胞和细胞外功能具有深远的影响,首先是细胞迁移。在这里,我们描述了一组最近的结果,这些结果扩展了这一概念,并阐明了胞吞基质如何动态控制迁移策略的可塑性。我们进一步强调了细胞器接触位点对迁移的影响以及细胞器定位在这一过程中的作用。最后,我们说明了全局扰动胞吞循环如何影响细胞和细胞外力学,最终控制迁移模式从固态到液态样的转变,这可能对癌症扩散产生影响。