Substrate stiffness regulates temporary NF-κB activation via actomyosin contractions
Substrate stiffness regulates temporary NF-κB activation via actomyosin contractions
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DOI：
10.1016/j.yexcr.2013.09.018
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发表时间：
2013-11-15
影响因子：
3.7
通讯作者：
Haga, Hisashi
中科院分区：
文献类型：
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作者：
Ishihara, Seiichiro;Yasuda, Motoaki;Haga, Hisashi
细胞外基质(ECM)的物理性质可以通过机械转导来控制细胞表型，机械转导是将机械应力转化为生化信号的过程。虽然目前的研究正在澄清机械转导与细胞骨架或黏附复合体之间的关系，但转录因子对机械转导的作用还不是很清楚。这项研究的结果表明，转录因子NF-kappa B是免疫反应和癌症进展的主要调节因子，对底物刚性有反应。生长在硬基质上的H1299肺腺癌细胞暂时被诱导了核因子-kappaB的激活，而在软基质上生长的细胞却没有被诱导活化。尽管NF-kappa B的激活不依赖于细胞外基质结合蛋白整合素β1的活性，但这种激活依赖于肌球蛋白调节轻链(MRLC)的磷酸化所诱导的肌球蛋白收缩。此外，Rho激酶抑制剂Y27632抑制MRLC的磷酸化降低了核因子-kappa B的活性。我们还观察到了细胞的底物特异性形态，生长在软底物上的细胞看起来更圆，生长在硬底物上的细胞看起来更平展。抑制核因子-kappaB的激活会导致两种底物上这些形态的逆转。这些结果表明，底物硬度通过肌动球蛋白收缩来调节核因子-kappaB的活性，导致形态变化。(C)2013 Elsevier Inc.保留所有权利。
Physical properties of the extracellular matrix (ECM) can control cellular phenotypes via mechanotransduction, which is the process of translation of mechanical stresses into biochemical signals. While current research is clarifying the relationship between mechanotransduction and cytoskeleton or adhesion complexes, the contribution of transcription factors to mechanotransduction is not well understood. The results of this study revealed that the transcription factor NF-kappa B, a major regulator for immunoreaction and cancer progression, is responsive to substrate stiffness. NF-kappa B activation was temporarily induced in H1299 lung adenocarcinoma cells grown on a stiff substrate but not in cells grown on a soft substrate. Although the activation of NF-kappa B was independent of the activity of integrin beta 1, an ECM-binding protein, the activation was dependent on actomyosin contractions induced by phosphorylation of myosin regulatory light chain (MRLC). Additionally, the inhibition of MRLC phosphorylation by Rho kinase inhibitor Y27632 reduced the activity of NF-kappa B. We also observed substrate-specific morphology of the cells, with cells grown on the soft substrate appearing more rounded and cells grown on the stiff substrate appearing more spread out. Inhibiting NF-kappa B activation caused a reversal of these morphologies on both substrates. These results suggest that substrate stiffness regulates NF-kappa B activity via actomyosin contractions, resulting in morphological changes. (C) 2013 Elsevier Inc. All rights reserved.