Nesprin-1 impact on tumorigenic cell phenotypes

Mol Biol Rep. 2020 Feb;47(2):921-934. doi: 10.1007/s11033-019-05184-w. Epub 2019 Nov 18.

Abstract

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.

Keywords: Cancer; Cellular senescence; Genome stability; Nesprin-1; Nuclear envelope.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Microfilament Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism
  • Phenotype

Substances

  • Actins
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • SYNE1 protein, human