Mechanics and Genetics of Embryonic and Tumor Development Group, Institut Curie, PSL Research University, Centre National de la Recherche Scientifique, UMR168, Inserm, Sorbonne Universities, Paris, France.
Mechanics and Genetics of Embryonic and Tumor Development Group, Institut Curie, PSL Research University, Centre National de la Recherche Scientifique, UMR168, Inserm, Sorbonne Universities, Paris, France
J Cell Biol. 2018 May 7;217(5):1571-1587. doi: 10.1083/jcb.201701039. Epub 2018 Feb 21.
Cancer has been characterized as a genetic disease, associated with mutations that cause pathological alterations of the cell cycle, adhesion, or invasive motility. Recently, the importance of the anomalous mechanical properties of tumor tissues, which activate tumorigenic biochemical pathways, has become apparent. This mechanical induction in tumors appears to consist of the destabilization of adult tissue homeostasis as a result of the reactivation of embryonic developmental mechanosensitive pathways in response to pathological mechanical strains. These strains occur in many forms, for example, hypervascularization in late tumors leads to high static hydrodynamic pressure that can promote malignant progression through hypoxia or anomalous interstitial liquid and blood flow. The high stiffness of tumors directly induces the mechanical activation of biochemical pathways enhancing the cell cycle, epithelial-mesenchymal transition, and cell motility. Furthermore, increases in solid-stress pressure associated with cell hyperproliferation activate tumorigenic pathways in the healthy epithelial cells compressed by the neighboring tumor. The underlying molecular mechanisms of the translation of a mechanical signal into a tumor inducing biochemical signal are based on mechanically induced protein conformational changes that activate classical tumorigenic signaling pathways. Understanding these mechanisms will be important for the development of innovative treatments to target such mechanical anomalies in cancer.
癌症已被定义为一种遗传疾病，与导致细胞周期、黏附和侵袭运动等病理性改变的突变有关。最近，肿瘤组织异常力学特性在激活肿瘤发生的生化途径方面的重要性已变得明显。这种肿瘤中的机械诱导似乎包括由于对病理性机械应变的反应，胚胎发育的机械敏感途径的重新激活，导致成年组织内稳态的不稳定。这些应变以多种形式出现，例如，晚期肿瘤中的过度血管化会导致高静态流体静压力，这可能通过缺氧或异常的间质液体和血流促进恶性进展。肿瘤的高硬度直接诱导生化途径的机械激活，增强细胞周期、上皮-间充质转化和细胞运动。此外，与细胞过度增殖相关的固体压的增加会激活受相邻肿瘤压迫的健康上皮细胞中的肿瘤发生途径。将机械信号转化为诱导肿瘤发生的生化信号的潜在分子机制基于机械诱导的蛋白质构象变化，这些变化会激活经典的肿瘤发生信号通路。了解这些机制对于开发针对癌症中这种机械异常的创新治疗方法非常重要。
