EMT-Induced Cell-Mechanical Changes Enhance Mitotic Rounding Strength.

EMT-Induced Cell-Mechanical Changes Enhance Mitotic Rounding Strength.
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DOI:
10.1002/advs.202001276
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发表时间:
2020-10
期刊:
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子:
--
通讯作者:
Fischer-Friedrich E
Fischer-Friedrich E
中科院分区:
其他
文献类型:
--
作者:
Hosseini K;Taubenberger A;Werner C;Fischer-Friedrich E

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为了成功地进行有丝分裂,大多数动物细胞需要获得圆形以为有丝分裂纺锤体提供空间。这种有丝分裂的圆缩依赖于周围组织的机械变形,并由肌动球蛋白收缩力驱动。癌细胞能够在机械挑战的环境中保持成功的有丝分裂,例如肿瘤生长的日益拥挤的环境,因此,表明癌症中有丝分裂圆切的能力增强。研究表明,上皮-间质转化(EMT)是癌症进展和转移的标志,可引起乳腺上皮细胞的细胞力学变化。这些变化在间期和有丝分裂中是相反的,对应于有丝分裂的圆形强度增强。此外,研究表明,细胞力学变化与EMT诱导的Rho GTPases RhoA和Rac1活性的强烈变化相关。因此,我们发现Rac1抑制可以挽救EMT诱导的皮质机械表型。这些发现暗示了EMT在机械受限环境(如生长中的肿瘤)中成功的有丝分裂成圆和分裂中的新作用。为了成功分裂,大多数动物细胞在有丝分裂中需要获得圆形。研究表明,上皮-间质转化(EMT)引起乳腺上皮细胞的细胞力学变化和有丝分裂圆缩增强。这些发现暗示了EMT在机械受限环境(如生长中的肿瘤)中成功的有丝分裂成圆和分裂中的新作用。
To undergo mitosis successfully, most animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, it is shown that the epithelial–mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to cell‐mechanical changes in breast epithelial cells. These changes are opposite in interphase and mitosis and correspond to an enhanced mitotic rounding strength. Furthermore, it is shown that cell‐mechanical changes correlate with a strong EMT‐induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, it is found that Rac1 inhibition rescues the EMT‐induced cortex‐mechanical phenotype. The findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor. To divide successfully, most animal cells need to acquire a round shape in mitosis. It is shown that the epithelial–mesenchymal transition (EMT) gives rise to cell‐mechanical changes and enhanced mitotic rounding in breast epithelial cells. The findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as growing tumors.
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