Mechanotransduction in tumor progression: The dark side of the force.
Mechanotransduction in tumor progression: The dark side of the force.
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DOI：
10.1083/jcb.201701039
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发表时间：
2018-05-07
期刊：
影响因子：
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通讯作者：
Farge E
中科院分区：
文献类型：
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作者：
Broders-Bondon F;Nguyen Ho-Bouldoires TH;Fernandez-Sanchez ME;Farge E
布罗德斯-邦登等人。回顾肿瘤组织的病理力学特性，以及在肿瘤进展过程中异常的机械信号如何导致致癌生化信号。癌症被认为是一种遗传性疾病，与引起细胞周期、粘附或侵袭性运动病理改变的突变有关。最近，激活致瘤生化途径的肿瘤组织异常机械特性的重要性已经变得显而易见。肿瘤中的这种机械诱导似乎包括成人组织稳态的不稳定，这是由于胚胎发育机械敏感途径响应病理性机械应变而重新激活的结果。这些菌株以多种形式出现，例如，晚期肿瘤中的血管过多会导致高静态流体动力压力，从而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、上皮间质转化和细胞运动。此外，与细胞过度增殖相关的固体应力压力的增加会激活被邻近肿瘤压缩的健康上皮细胞的致瘤途径。将机械信号转化为肿瘤诱导生化信号的基本分子机制是基于机械诱导的蛋白质构象变化，该变化激活经典的致瘤信号通路。了解这些机制对于开发针对癌症中此类机械异常的创新疗法非常重要。
Broders-Bondon et al. review the pathological mechanical properties of tumor tissues and how abnormal mechanical signals result in oncogenic biochemical signals during tumor progression. 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.
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影响因子：
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作者：
Bonan S;Albrengues J;Grasset E;Kuzet SE;Nottet N;Bourget I;Bertero T;Mari B;Meneguzzi G;Gaggioli C
通讯作者：
Gaggioli C
影响因子：
1.6
作者：
Branum, Sylvia R.;Yamada-Fisher, Miho;Burggren, Warren
通讯作者：
Burggren, Warren
影响因子：
3.4
作者：
Brujic, Jasna;Hermans, Rodolfo I. Z.;Fernandez, Julio M.
通讯作者：
Fernandez, Julio M.
影响因子：
4.1
作者：
Cassereau, Luke;Miroshnikova, Yekaterina A.;Ou, Guanqing;Lakins, Johnathon;Weaver, Valerie M.
通讯作者：
Weaver, Valerie M.
影响因子：
21.3
作者：
通讯作者：
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