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靶向肌动蛋白细胞骨架重组对正常细胞和恶性细胞力学特性的不同影响。

Distinct impact of targeted actin cytoskeleton reorganization on mechanical properties of normal and malignant cells.

作者信息

Efremov Yu M, Dokrunova A A, Efremenko A V, Kirpichnikov M P, Shaitan K V, Sokolova O S

机构信息

M.V. Lomonosov Moscow State University, Faculty of Biology, 119234, 1/73 Leninskie Gory, Moscow, Russia.

M.V. Lomonosov Moscow State University, Faculty of Biology, 119234, 1/73 Leninskie Gory, Moscow, Russia.

出版信息

Biochim Biophys Acta. 2015 Nov;1853(11 Pt B):3117-25. doi: 10.1016/j.bbamcr.2015.05.008. Epub 2015 May 10.

DOI:10.1016/j.bbamcr.2015.05.008
PMID:25970206
Abstract

The actin cytoskeleton is substantially modified in cancer cells because of changes in actin-binding protein abundance and functional activity. As a consequence, cancer cells have distinctive motility and mechanical properties, which are important for many processes, including invasion and metastasis. Here, we studied the effects of actin cytoskeleton alterations induced by specific nucleation inhibitors (SMIFH2, CK-666), cytochalasin D, Y-27632 and detachment from the surface by trypsinization on the mechanical properties of normal Vero and prostate cancer cell line DU145. The Young's modulus of Vero cells was 1300±900 Pa, while the prostate cancer cell line DU145 exhibited significantly lower Young's moduli (600±400 Pa). The Young's moduli exhibited a log-normal distribution for both cell lines. Unlike normal cells, cancer cells demonstrated diverse viscoelastic behavior and different responses to actin cytoskeleton reorganization. They were more resistant to specific formin-dependent nucleation inhibition, and reinforced their cortical actin after detachment from the substrate. This article is part of a Special Issue entitled: Mechanobiology.

摘要

由于肌动蛋白结合蛋白丰度和功能活性的变化,癌细胞中的肌动蛋白细胞骨架发生了显著改变。因此,癌细胞具有独特的运动性和力学特性,这对包括侵袭和转移在内的许多过程都很重要。在此,我们研究了由特定成核抑制剂(SMIFH2、CK-666)、细胞松弛素D、Y-27632以及胰蛋白酶消化使其脱离表面所诱导的肌动蛋白细胞骨架改变对正常Vero细胞和前列腺癌细胞系DU145力学特性的影响。Vero细胞的杨氏模量为1300±900 Pa,而前列腺癌细胞系DU145的杨氏模量显著更低(600±400 Pa)。两种细胞系的杨氏模量均呈现对数正态分布。与正常细胞不同,癌细胞表现出多样的粘弹性行为以及对肌动蛋白细胞骨架重组的不同反应。它们对特定的formin依赖性成核抑制更具抗性,并且在从底物脱离后会增强其皮质肌动蛋白。本文是名为《机械生物学》的特刊的一部分。

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