Nuclear mechanics in cancer.
Nuclear mechanics in cancer.
复制标题
DOI：
10.1007/978-1-4899-8032-8_20
复制
发表时间：
2014
影响因子：
--
通讯作者：
Lammerding J
中科院分区：
文献类型：
--
作者：
Denais C;Lammerding J
尽管经过数十年的研究，癌症转移仍然是一个不完全理解的过程，既复杂又具有破坏性。近年来，人们越来越多地推动对肿瘤发生的生物力学方面的研究，以补充对遗传和生化变化的研究。与癌细胞中遇到的高遗传变异性相反，几乎所有转移性细胞在离开原发性肿瘤、侵入周围组织、通过循环系统并最终渗入新组织时都受到相同的物理约束。活细胞成像和其他生物物理技术的进步，包括亚细胞力学的测量，已经对癌细胞的物理学产生了惊人的新见解。虽然大部分研究都集中在细胞骨架和细胞微环境的力学上，但现在出现的是，细胞核的机械特性及其与细胞骨架的连接可能在癌症转移中起主要作用，因为大而硬的细胞核的变形在通过致密的间隙空间和狭窄的毛细血管期间呈现实质性障碍。在这里，我们提出了一个概述的分子组成，管理的机械性能的细胞核，我们讨论了如何在许多癌症中观察到的核结构和组成的变化可以调节核力学和促进转移过程。对核力学和转移进展之间的这种相互作用的更深入的了解可能在癌症诊断和治疗中具有强大的意义，并可能揭示用于药理学抑制癌细胞侵袭的新的治疗靶点。
Despite decades of research, cancer metastasis remains an incompletely understood process that is as complex as it is devastating. In recent years, there has been an increasing push to investigate the biomechanical aspects of tumorigenesis, complementing the research on genetic and biochemical changes. In contrast to the high genetic variability encountered in cancer cells, almost all metastatic cells are subject to the same physical constraints as they leave the primary tumor, invade surrounding tissues, transit through the circulatory system, and finally infiltrate new tissues. Advances in live cell imaging and other biophysical techniques, including measurements of subcellular mechanics, have yielded stunning new insights into the physics of cancer cells. While much of this research has been focused on the mechanics of the cytoskeleton and the cellular microenvironment, it is now emerging that the mechanical properties of the cell nucleus and its connection to the cytoskeleton may play a major role in cancer metastasis, as deformation of the large and stiff nucleus presents a substantial obstacle during the passage through the dense interstitial space and narrow capillaries. Here, we present an overview of the molecular components that govern the mechanical properties of the nucleus and we discuss how changes in nuclear structure and composition observed in many cancers can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between nuclear mechanics and metastatic progression may have powerful implications in cancer diagnostics and therapy and may reveal novel therapeutic targets for pharmacological inhibition of cancer cell invasion.