Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, California 94143; email:
Joint Graduate Group in Bioengineering (University of California, San Francisco, and University of California, Berkeley), San Francisco, California 94143.
Annu Rev Cell Dev Biol. 2016 Oct 6;32:527-554. doi: 10.1146/annurev-cellbio-111315-125150. Epub 2016 Jun 8.
Mechanical force modulates development, influences tissue homeostasis, and contributes to disease. Forces sculpt tissue-level behaviors and direct cell fate by engaging mechanoreceptors and by altering organization of the cytoskeleton and actomyosin contractility to stimulate mechanotransduction mechanisms that alter transcription. Nevertheless, how force specifically leverages mechanotransduction pathways to control transcriptional regulation of cell fate remains unclear. Here we review recent findings specifically in the context of epithelial-to-mesenchymal transitions that have revealed conserved mechanisms whereby extracellular force, mediated through cell-extracellular matrix and cell-cell junctional complexes, induces transcriptional reprogramming to alter cell and tissue fate. We focus on the interplay between tissue mechanics and the epithelial-to-mesenchymal transitions that occur during embryonic development and cancer malignancy. We describe the adhesion-linked cellular machinery that mediates mechano-transduction and elaborate on how these force-linked networks stimulate key transcriptional programs that induce an epithelial-to-mesenchymal phenotypic transition, thereby providing an overview of how mechanical signals can be translated into a change in cell fate.
机械力调节发育、影响组织稳态，并有助于疾病发生。力通过与机械感受器相互作用，并通过改变细胞骨架和肌动球蛋白收缩性的组织来塑造组织水平的行为并指导细胞命运，从而刺激改变转录的机械转导机制。然而，力如何具体利用机械转导途径来控制细胞命运的转录调控尚不清楚。在这里，我们特别回顾了上皮-间充质转化的最新发现，这些发现揭示了细胞外力通过细胞-细胞外基质和细胞-细胞连接复合物介导的保守机制，诱导转录重编程以改变细胞和组织命运。我们重点介绍了组织力学与胚胎发育和癌症恶性期间发生的上皮-间充质转化之间的相互作用。我们描述了介导机械转导的黏附连接细胞机制，并详细阐述了这些力相关网络如何刺激关键转录程序，诱导上皮-间充质表型转化，从而概述了机械信号如何转化为细胞命运的变化。
