Apical cell protrusions cause vertical deformation of the soft cancer nucleus
Apical cell protrusions cause vertical deformation of the soft cancer nucleus
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DOI：
10.1002/jcp.28672
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Lele, Tanmay P.
中科院分区：
文献类型：
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作者：
Kent, Ian A.;Zhang, Qiao;Lele, Tanmay P.
乳腺癌细胞核具有高度不规则的形状，这是乳腺癌进展的诊断和预后标志物。不规则癌核形状发展的机制还不清楚。在这里，我们报告的存在垂直，顶端细胞突起培养的MDA-MB-231乳腺癌细胞。一旦形成，这些突起持续数小时的时间尺度，并与垂直向上的核变形。它们在正常乳腺上皮细胞（MCF-10A细胞）中不存在。与MCF-10A细胞相比，微管破坏优先在MDA-MB-231细胞中富集这些突起，而抑制非肌肉肌球蛋白II（NMMII）则消除了这种富集。垂直细胞和核形状的动态共聚焦成像显示，顶端细胞突起首先形成，并且作为响应，核变形和/或随后垂直挤出到顶端突起中。核纤层蛋白A/C在MDA-MB-231细胞中的过表达减少了顶端突起的核变形。这些数据突出了移动边界产生的机械应力以及异常核力学在乳腺癌细胞异常核形状发展中的作用。
Breast cancer nuclei have highly irregular shapes, which are diagnostic and prognostic markers of breast cancer progression. The mechanisms by which irregular cancer nuclear shapes develop are not well understood. Here we report the existence of vertical, apical cell protrusions in cultured MDA-MB-231 breast cancer cells. Once formed, these protrusions persist over time scales of hours and are associated with vertically upward nuclear deformations. They are absent in normal mammary epithelial cells (MCF-10A cells). Microtubule disruption enriched these protrusions preferentially in MDA-MB-231 cells compared with MCF-10A cells, whereas inhibition of nonmuscle myosin II (NMMII) abolished this enrichment. Dynamic confocal imaging of the vertical cell and nuclear shape revealed that the apical cell protrusions form first, and in response, the nucleus deforms and/or subsequently gets vertically extruded into the apical protrusion. Overexpression of lamin A/C in MDA-MB-231 cells reduced nuclear deformation in apical protrusions. These data highlight the role of mechanical stresses generated by moving boundaries, as well as abnormal nuclear mechanics in the development of abnormal nuclear shapes in breast cancer cells.