PNAS：致癌基因会“硬化”细胞

      日前，来自瑞典卡罗琳医学院的研究人员证实，致癌基因会增强癌细胞的硬度和扩散能力。这为肿瘤诊断和治疗提供了更有效的依据。这一研究成果已发表在新一期美国《国家科学院学报》（PNAS）上。

        研究人员通过先进的显微技术发现，致癌基因能改变细胞内的波形蛋白纤维组织骨架的形状，诱导细胞硬度增加，同时使细胞向周边侵袭、扩散的能力更强。

        此外，他们还发现，一个名为 HDAC6 的蛋白质是产生上述变化的关键因素，它能导致波形蛋白骨架结构重组和增强细胞硬度。

        研究人员表示，这一成果揭示，癌细胞的机械特性（如硬度、空间形状等）对理解肿瘤发生和扩散的机理非常重要，也为今后癌症防治指明了更有针对性的方向。（转化医学网360zhyx.com）

原文链接：

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Oncogenes induce a vimentin filament collapse mediated by HDAC6 that is linked to cell stiffness

Oncogenes deregulate fundamental cellular functions, which can lead to development of tumors, tumor-cell invasion, and metastasis.As the mechanical properties of cells govern cell motility, we hypothesized that oncogenes promote cell invasion by inducing cytoskeletal changes that increase cellular stiffness. We show that the oncogenes simian virus 40 large T antigen, c-Myc,and cyclin E induce spatial reorganization of the vimentin intermediate filament network in cells. At the cellular level,      this reorganization manifests as increased width of vimentin fibers and the collapse of the vimentin network. At nanoscale        resolution, the organization of vimentin fibers in these oncogene-expressing cells was more entangled, with increased width     of the fibers compared with control cells. Expression of these oncogenes also resulted in up-regulation of the tubulin deacetylase histone deacetylase 6 (HDAC6) and altered spatial distribution of acetylated microtubules. This oncogene expression also induced  increases in cellular stiffness and promoted the invasive capacity of the cells. Importantly, HDAC6 was required and sufficient  for the structural collapse of the vimentin filament network, and was required for increased cellular stiffness of the oncogene-expressing cells. Taken together, these data are consistent with the possibility that oncogenes can induce cellular stiffness via an HDAC6-induced reorganization of the vimentin intermediate filament network.

来源：bio360