Feeling Stress: The Mechanics of Cancer Progression and Aggression.
Feeling Stress: The Mechanics of Cancer Progression and Aggression.
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DOI：
10.3389/fcell.2018.00017
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发表时间：
2018
影响因子：
5.5
通讯作者：
Weaver VM
中科院分区：
文献类型：
--
作者：
Northcott JM;Dean IS;Mouw JK;Weaver VM
肿瘤微环境是一个动态的景观，其中物理和机械特性在整个癌症进展过程中急剧演变。这些变化是由增强的肿瘤细胞收缩性和生长的肿瘤块的扩张以及通过改变周围细胞外基质（ECM）的材料性质驱动的。因此，肿瘤细胞暴露于许多不同的机械输入，包括细胞-细胞和细胞-ECM张力、压缩应力、间质液压力和剪切应力。癌基因参与响应于机械应力而被激活的信号传导途径，从而重新工作细胞对外源性机械刺激的内在响应，通过升高的肌动球蛋白收缩增强细胞内张力，并影响ECM硬度和组织形态。除了改变它们的细胞内张力和重塑微环境之外，细胞还通过基因表达的修饰对这些机械扰动表型做出积极响应。在此，我们描述了促进肿瘤进展和侵袭性的物理变化，讨论了它们的相互关系，并强调了新兴的治疗策略，以减轻推动癌症恶化的机械压力。
The tumor microenvironment is a dynamic landscape in which the physical and mechanical properties evolve dramatically throughout cancer progression. These changes are driven by enhanced tumor cell contractility and expansion of the growing tumor mass, as well as through alterations to the material properties of the surrounding extracellular matrix (ECM). Consequently, tumor cells are exposed to a number of different mechanical inputs including cell–cell and cell-ECM tension, compression stress, interstitial fluid pressure and shear stress. Oncogenes engage signaling pathways that are activated in response to mechanical stress, thereby reworking the cell's intrinsic response to exogenous mechanical stimuli, enhancing intracellular tension via elevated actomyosin contraction, and influencing ECM stiffness and tissue morphology. In addition to altering their intracellular tension and remodeling the microenvironment, cells actively respond to these mechanical perturbations phenotypically through modification of gene expression. Herein, we present a description of the physical changes that promote tumor progression and aggression, discuss their interrelationship and highlight emerging therapeutic strategies to alleviate the mechanical stresses driving cancer to malignancy.