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Ras 转化的和未转化的上皮细胞之间的机械失配。

Mechanical mismatch between Ras transformed and untransformed epithelial cells.

机构信息

Centre for Interdisciplinary NanoPhysics, Department of Physics, University of Ottawa, 598 King Edward, Ottawa, ON, K1N5N5 Canada.

出版信息

Soft Matter. 2017 Nov 22;13(45):8483-8491. doi: 10.1039/c7sm01396e.

DOI:10.1039/c7sm01396e
PMID:29091102
Abstract

The organization of the actin cytoskeleton plays a key role in regulating cell mechanics. It is fundamentally altered during transformation, affecting how cells interact with their environment. We investigated mechanical properties of cells expressing constitutively active, oncogenic Ras (Ras) in adherent and suspended states. To do this, we utilized atomic force microscopy and a microfluidic optical stretcher. We found that adherent cells stiffen and suspended cells soften with the expression of constitutively active Ras. The effect on adherent cells was reversed when contractility was inhibited with the ROCK inhibitor Y-27632, resulting in softer Ras cells. Our findings suggest that increased ROCK activity as a result of Ras has opposite effects on suspended and adhered cells. Our results also establish the importance of the activation of ROCK by Ras and its effect on cell mechanics.

摘要

细胞骨架的肌动蛋白组织在调节细胞力学方面起着关键作用。在转化过程中,它会发生根本改变,影响细胞与环境的相互作用。我们研究了在贴附和悬浮状态下表达组成性激活的致癌 Ras(Ras)的细胞的力学特性。为此,我们利用原子力显微镜和微流控光镊进行了研究。我们发现,表达组成性激活的 Ras 会使贴附细胞变硬,悬浮细胞变软。当用 ROCK 抑制剂 Y-27632 抑制收缩性时,贴附细胞的这种作用会被逆转,从而使 Ras 细胞变软。我们的研究结果表明,Ras 导致的 ROCK 活性增加对悬浮和贴附细胞有相反的影响。我们的研究结果还证实了 Ras 通过激活 ROCK 及其对细胞力学的影响的重要性。

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The role of RAS oncogenes in controlling epithelial mechanics.RAS 癌基因在控制上皮力学中的作用。
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Oncogenic instructs morphological transformation of human epithelia via differential tissue mechanics.
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Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue.各向异性应变的产生扰乱了宿主和致癌组织界面处野生型细胞的分裂。
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Oncogenic Signaling Alters Cell Shape and Mechanics to Facilitate Cell Division under Confinement.致癌信号改变细胞形状和力学特性,以促进受限环境下的细胞分裂。
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