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Transient nuclear envelope rupturing during interphase in human cancer cells

机译：人癌细胞间期的瞬时核膜破裂

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Neoplastic cells are often characterized by specific morphological abnormalities of the nuclear envelope (NE), which have been used for cancer diagnosis for more than a century. The NE is a double phospholipid bilayer that encapsulates the nuclear genome, regulates all nuclear trafficking of RNAs and proteins and prevents the passive diffusion of macromolecules between the nucleoplasm and the cytoplasm. Whether there is a consequence to the proper functioning of the cell and loss of structural integrity of the nucleus remains unclear. Using live cell imaging, we characterize a phenomenon wherein nuclei of several proliferating human cancer cell lines become temporarily ruptured during interphase. Strikingly, NE rupturing was associated with the mislocalization of nucleoplasmic and cytoplasmic proteins and, in the most extreme cases, the entrapment of cytoplasmic organelles in the nuclear interior. In addition, we observed the formation of micronuclei-like structures during interphase and the movement of chromatin out of the nuclear space. The frequency of these NE rupturing events was higher in cells in which the nuclear lamina, a network of intermediate filaments providing mechanical support to the NE, was not properly formed. Our data uncover the existence of a NE instability that has the potential to change the genomic landscape of cancer cells.
机译：肿瘤细胞通常特征在于核被膜（NE）的特定形态异常，已被用于癌症诊断超过一个世纪。 NE是双层磷脂双层，包裹着核基因组，调节RNA和蛋白质的所有核运输，并阻止大分子在核质和细胞质之间的被动扩散。尚不清楚细胞的正常功能和核结构完整性的丧失是否会导致后果。使用活细胞成像，我们表征了一种现象，其中几种增殖性人类癌细胞系的核在相间期暂时破裂。令人惊讶的是，NE破裂与核质和细胞质蛋白的错误定位有关，在最极端的情况下，与核内部细胞质细胞器的包裹有关。此外，我们观察到相间微核样结构的形成以及染色质移出核空间。这些NE破裂事件的频率在没有适当形成核薄层的细胞中较高，在这些细胞中，核薄层是为NE提供机械支撑的中间细丝网络。我们的数据揭示了NE不稳定性的存在，它可能会改变癌细胞的基因组格局。

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