文章：

紧张的情况：迫使肿瘤进展

A tense situation: forcing tumour progression

原文发布日期：2009-02-01

DOI: 10.1038/nrc2544

类型: Review Article

开放获取: 否

要点：

1. Cells within tissues are continuously exposed to physical forces, including hydrostatic pressure, shear stress and compression and tension forces. The nature of these forces can change in pathologies such as cardiovascular disease and cancer.
2. Cells sense force through mechanoreceptors and, regardless of the type of force applied, cells respond by exerting reciprocal actomyosin- and cytoskeleton-dependent cell-generated force by a process termed mechanoreciprocity.
3. Mechanoreciprocity maintains tensional homeostasis in the tissue and is necessary for development and tissue-specific differentiation. Its loss promotes disease progression, including liver fibrosis, atherosclerosis and cancer.
4. Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. This adaptation probably involves a combination of epigenetic chromatin remodelling events and direct physical links between the matrix and nucleus that regulate gene expression. These gene-regulatory processes are altered in diseases such as cancer.
5. Breast cancer is characterized by changes in cellular rheology and tissue level forces, a stiffening of the tissue and a progressive loss of tensional homeostasis that has been exploited to detect tumours. The mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk.

要点翻译：

1. 组织中的细胞持续受到物理力的作用，包括静水压、剪切应力以及压缩和拉伸力。在心血管疾病和癌症等病理状态下，这些力的性质会发生改变。
2. 细胞通过机械感受器感知外力，无论施加何种类型的力，细胞都会通过称为“机械互惠”的过程，施加由肌动-肌球蛋白和细胞骨架依赖的细胞源性力予以回应。
3. 机械互惠能维持组织的张力稳态，对发育和组织特异性分化至关重要。该机制的缺失会促进疾病进展，包括肝纤维化、动脉粥样硬化和癌症。
4. 细胞通过改变自身行为和重塑微环境来动态适应机械力。这种适应可能涉及表观遗传染色质重塑事件，以及基质与细胞核之间调节基因表达的直接物理连接。这些基因调控过程在癌症等疾病中会发生改变。
5. 乳腺癌的特征包括细胞流变学和组织层面力学特性的改变、组织硬化以及张力稳态的逐步丧失——这些特征已被用于肿瘤检测。组织的机械特性不仅促进疾病进展、影响治疗效果，还可能改变癌症发病风险。

英文摘要：

Cells within tissues are continuously exposed to physical forces including hydrostatic pressure, shear stress, and compression and tension forces. Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. They also sense these forces through mechanoreceptors and respond by exerting reciprocal actomyosin- and cytoskeletal-dependent cell-generated force by a process termed 'mechanoreciprocity'. Loss of mechanoreciprocity has been shown to promote the progression of disease, including cancer. Moreover, the mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk. Thus, the changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis.

摘要翻译： 

组织内的细胞持续受到包括静水压、剪切力以及压缩和牵张力在内的物理力作用。细胞通过改变自身行为并重塑微环境，动态适应这些外力。它们还通过机械感受器感知这些力量，并通过肌动蛋白-肌球蛋白和细胞骨架依赖的方式施加反向的细胞自身产生的力，这一过程称为“机械互作”。机械互作的丧失已被证实可促进包括癌症在内的疾病进展。此外，组织的力学特性也会推动疾病进展、影响治疗效果，甚至可能改变癌症风险。因此，在试图理解肿瘤发生这一复杂过程时，必须考虑细胞所经历的不断变化的力量。

原文链接：

A tense situation: forcing tumour progression