EMT induces characteristic changes of Rho GTPases and downstream effectors with a mitosis-specific twist.

IF 2 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Physical biology Pub Date : 2023-09-12 DOI:10.1088/1478-3975/acf5bd

Kamran Hosseini, Annika Frenzel, Elisabeth Fischer-Friedrich

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引用次数: 0

Abstract

Epithelial-mesenchymal transition (EMT) is a key cellular transformation for many physiological and pathological processes ranging from cancer over wound healing to embryogenesis. Changes in cell migration, cell morphology and cellular contractility were identified as hallmarks of EMT. These cellular properties are known to be tightly regulated by the actin cytoskeleton. EMT-induced changes of actin-cytoskeletal regulation were demonstrated by previous reports of changes of actin cortex mechanics in conjunction with modifications of cortex-associated f-actin and myosin. However, at the current state, the changes of upstream actomyosin signaling that lead to corresponding mechanical and compositional changes of the cortex are not well understood. In this work, we show in breast epithelial cancer cells MCF-7 that EMT results in characteristic changes of the cortical association of Rho-GTPases Rac1, RhoA and RhoC and downstream actin regulators cofilin, mDia1 and Arp2/3. In the light of our findings, we propose that EMT-induced changes in cortical mechanics rely on two hitherto unappreciated signaling paths-i) an interaction between Rac1 and RhoC and ii) an inhibitory effect of Arp2/3 activity on cortical association of myosin II.

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EMT通过有丝分裂特异性扭曲诱导Rho-GTP酶和下游效应物的特征性变化。

上皮-间质转化（EMT）是许多生理和病理过程的关键细胞转化，从癌症伤口愈合到胚胎发生。细胞迁移、细胞形态和细胞收缩性的变化被确定为EMT的特征。众所周知，这些细胞特性受到肌动蛋白细胞骨架的严格调控。EMT诱导的肌动蛋白细胞骨架调节的变化已被先前关于肌动蛋白皮层力学的变化以及皮层相关的f-肌动蛋白和肌球蛋白的修饰的报道所证实。然而，在目前的状态下，导致皮层相应的机械和组成变化的上游肌动蛋白信号的变化尚不清楚。在这项工作中，我们在乳腺上皮癌症细胞MCF-7中显示，EMT导致Rho-GTP酶Rac1、RhoA和RhoC以及下游肌动蛋白调节因子cofilin、mDia1和Arp2/3的皮层结合的特征性变化。根据我们的发现，我们提出EMT诱导的皮层力学变化依赖于两种迄今为止未被重视的信号通路——i）Rac1和RhoC之间的相互作用，以及ii）Arp2/3活性对肌球蛋白ii的皮层结合的抑制作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Physical biology 生物-生物物理

CiteScore

4.20

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Physical Biology publishes articles in the broad interdisciplinary field bridging biology with the physical sciences and engineering. This journal focuses on research in which quantitative approaches – experimental, theoretical and modeling – lead to new insights into biological systems at all scales of space and time, and all levels of organizational complexity. Physical Biology accepts contributions from a wide range of biological sub-fields, including topics such as: molecular biophysics, including single molecule studies, protein-protein and protein-DNA interactions subcellular structures, organelle dynamics, membranes, protein assemblies, chromosome structure intracellular processes, e.g. cytoskeleton dynamics, cellular transport, cell division systems biology, e.g. signaling, gene regulation and metabolic networks cells and their microenvironment, e.g. cell mechanics and motility, chemotaxis, extracellular matrix, biofilms cell-material interactions, e.g. biointerfaces, electrical stimulation and sensing, endocytosis cell-cell interactions, cell aggregates, organoids, tissues and organs developmental dynamics, including pattern formation and morphogenesis physical and evolutionary aspects of disease, e.g. cancer progression, amyloid formation neuronal systems, including information processing by networks, memory and learning population dynamics, ecology, and evolution collective action and emergence of collective phenomena.