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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.

Original publication

DOI

10.1007/s11033-019-05184-w

Type

Journal article

Journal

Mol biol rep

Publication Date

02/2020

Volume

47

Pages

921 - 934

Keywords

Cancer, Cellular senescence, Genome stability, Nesprin-1, Nuclear envelope, Actins, Carcinogenesis, Cell Line, Tumor, Cell Nucleus, Cytoskeletal Proteins, Gene Expression, Gene Expression Regulation, Neoplastic, Humans, Microfilament Proteins, Nerve Tissue Proteins, Nuclear Envelope, Phenotype