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黏着斑激酶在调节细胞力学性质中的作用。

The role of focal adhesion kinase in the regulation of cellular mechanical properties.

机构信息

Faculty of Physics and Earth Science, Institute of Experimental Physics I, Biological Physics Division, University of Leipzig, Linnéstr. 5, D-04103 Leipzig, Germany.

出版信息

Phys Biol. 2013 Dec;10(6):065005. doi: 10.1088/1478-3975/10/6/065005. Epub 2013 Dec 4.

Abstract

The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

摘要

机械性能的调节对于细胞侵入结缔组织或通过血液或淋巴管的内皮进行的细胞内和细胞外渗至关重要。细胞侵入对于许多健康过程的调节是重要的,如免疫反应和伤口愈合。此外,细胞侵入在与疾病相关的过程中发挥作用,如肿瘤转移和自身免疫反应。到目前为止,黏着斑激酶(FAK)在调节细胞的机械性能及其对细胞侵入效率的影响方面的作用仍然不清楚。因此,这篇综述重点介绍了 FAK 调节细胞机械性能的作用,以及与机械调节蛋白黏着斑激酶(FAK)的关系。此外,它还指出了 FAK 与癌症细胞侵入和转移之间的联系,表明 FAK 调节了细胞运动所需的细胞机械性能。此外,FAK 通过与桩蛋白结合,间接影响黏着斑激酶与黏着斑蛋白的结合,从而破坏黏着斑蛋白与黏着斑蛋白的结合。此外,这篇综述强调了 FAK 是否具有与黏着斑激酶类似的调节功能。特别是,它讨论了 FAK 和黏着斑激酶在调节细胞生物力学特性方面的差异和相似之处。最后,本文强调了这两种黏着斑蛋白,黏着斑激酶和 FAK,协同发挥作用,调节细胞的机械性能,如刚度和收缩力。随后,这些机械性能决定了细胞侵入组织的能力,并为未来抑制过度细胞侵入和转移形成的药物开发提供了一个来源和汇点。

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