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Nesprin-1 impact on tumorigenic cell phenotypes

  • Ilknur Sur-ErdemEmail author
  • Muhammed Sajid Hussain
  • Maria Asif
  • Nareg Pınarbası
  • Ali Cenk Aksu
  • Angelika A. Noegel
Original Article
  • 110 Downloads

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

Nuclear envelope Nesprin-1 Genome stability Cancer Cellular senescence 

Notes

Acknowledgements

We thank to Dr. Reena Buurman for providing the THLE-2 cells, Rolf Müller for cloning, Dr. V. S. Peche for helping at various stages of this work, and Berthold Gaβen for providing antibodies. The authors gratefully acknowledge the use of services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget. The work was supported by the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD).

Compliance with ethical standards

Conflict of interest

All the authors declare that they do not have any competing interests.

Supplementary material

11033_2019_5184_MOESM1_ESM.docx (4.6 mb)
Supplementary material 1 (DOCX 4709 kb)

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Institute of Biochemistry I, Medical FacultyUniversity Hospital CologneCologneGermany
  2. 2.Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of CologneCologneGermany
  3. 3.Koç University School of MedicineIstanbulTurkey
  4. 4.Koç University Research Center for Translational Medicine (KUTTAM)IstanbulTurkey
  5. 5.Cologne Center for Genomics (CCG)University of CologneCologneGermany

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