Institute of Biochemistry I, Medical Faculty, University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Mol Biol Rep. 2020 Feb;47(2):921-934. doi: 10.1007/s11033-019-05184-w. Epub 2019 Nov 18.
The largest protein of the nuclear envelope (NE) is Nesprin-1 which forms a network along the NE interacting with actin, Emerin, Lamin, and SUN proteins. Mutations in the SYNE1 gene and reduction in Nesprin-1 protein levels have been reported to correlate with several age related diseases and cancer. In the present study, we tested whether Nesprin-1 overexpression can reverse the malignant phenotype of Huh7 cells, a human liver cancer cell line, which carries a mutation in the SYNE1 gene resulting in reduced Nesprin-1 protein levels, has altered nuclear shape, altered amounts and localization of NE components, centrosome localization and genome stability. Ectopic expression of a mini-Nesprin-1 led to an improvement of the nuclear shape, corrected the mislocalization of NE proteins, the centrosome positioning, and the alterations in the DNA damage response network. Additionally, Nesprin-1 had a profound effect on cellular senescence. These findings suggest that Nesprin-1 may be effective in tumorigenic cell phenotype correction of human liver cancer.
核膜（NE）的最大蛋白是 nesprin-1，它沿着与肌动蛋白、Emerin、 lamin 和 SUN 蛋白相互作用的 NE 形成网络。已有报道称，SYNE1 基因突变和 nesprin-1 蛋白水平降低与几种与年龄相关的疾病和癌症相关。在本研究中，我们测试了 nesprin-1 过表达是否可以逆转 Huh7 细胞（一种携带 SYNE1 基因突变导致 nesprin-1 蛋白水平降低的人肝癌细胞系）的恶性表型，该细胞具有改变的核形状、改变的核膜成分的数量和定位、中心体定位和基因组稳定性。外源性表达一种 mini-Nesprin-1 可改善核形状，纠正核膜蛋白的定位错误、中心体定位和 DNA 损伤反应网络的改变。此外，nesprin-1 对细胞衰老有深远的影响。这些发现表明，nesprin-1 可能对人肝癌的致瘤细胞表型校正有效。
