Segarra Daniel T, Yavorski John M, Blanck George
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Biomed Rep. 2017 Aug;7(2):163-168. doi: 10.3892/br.2017.940. Epub 2017 Jul 6.
Initial reports of the role of the cytoskeleton in cancer indicated that tumor cells with a more disorganized cytoskeleton were more tumorigenic. These reports were based on stains for the F-actin cytoskeleton, for example, using phalloidin or anti-F-actin antibody reagents, and gave a basic impression of F-actin-based cytoskeletal integrity. Later developments emphasized the significance of the cytoskeletal elements in cell migration, presumably associated with either basement membrane invasion or metastasis, or both, with several specific proteins implicated in the formation of cell invadopodia. With the advent of genomics approaches, it has become clear that cytoskeletal related proteins are indeed common targets of mutagenesis in cancer and commonly rank among the most mutated proteins in cancers, presumably due to large coding region sizes and the significant stochastic component to human mutagenesis. This cytoskeletal genomics result is consistent with the loss of cytoskeleton integrity as a hallmark of tumor development, but raises the question of whether such mutational sensitivity relates to the migration and invadopodia aspects of tumor progression. In the present study, the authors report that it is possible to identify a set of cytoskeletal related proteins protected from mutation, in comparison to the commonly mutated cytoskeleton related proteins in certain, but not all cancer, datasets.
关于细胞骨架在癌症中作用的初步报告表明，细胞骨架更紊乱的肿瘤细胞具有更强的致瘤性。这些报告基于对F-肌动蛋白细胞骨架的染色，例如使用鬼笔环肽或抗F-肌动蛋白抗体试剂，给出了基于F-肌动蛋白的细胞骨架完整性的基本印象。后来的研究进展强调了细胞骨架成分在细胞迁移中的重要性，推测这与基底膜侵袭或转移或两者都有关，有几种特定蛋白质与细胞侵袭伪足的形成有关。随着基因组学方法的出现，很明显细胞骨架相关蛋白确实是癌症中诱变的常见靶点，并且通常在癌症中最易突变的蛋白中名列前茅，这可能是由于编码区较大以及人类诱变中存在显著的随机成分。这种细胞骨架基因组学结果与细胞骨架完整性丧失作为肿瘤发展的标志是一致的，但提出了这样一个问题，即这种突变敏感性是否与肿瘤进展的迁移和侵袭伪足方面有关。在本研究中，作者报告说，与某些（但不是所有）癌症数据集中常见突变的细胞骨架相关蛋白相比，有可能识别出一组受保护不发生突变的细胞骨架相关蛋白。
