Research Papers:

Silencing of the nucleocytoplasmic shuttling protein karyopherin a2 promotes cell-cycle arrest and apoptosis in glioblastoma multiforme

Ramon Martinez-Olivera, Angeliki Datsi, Maren Stallkamp, Manfred Köller, Isabelle Kohtz, Bogdan Pintea and Konstantinos Gousias _

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Oncotarget. 2018; 9:33471-33481. https://doi.org/10.18632/oncotarget.26033

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Ramon Martinez-Olivera1,*, Angeliki Datsi2,3,*, Maren Stallkamp2,4, Manfred Köller5, Isabelle Kohtz2, Bogdan Pintea1 and Konstantinos Gousias1,2,4,6

1Department of Neurosurgery and Neurotraumatology, BG University Hospital Bergmannsheil, 44789 Bochum, Germany

2Department of Laboratory for Neurosurgical Research, BG University Hospital Bergmannsheil, 44789 Bochum, Germany

3Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine University, 40225 Düsseldorf, Germany

4Medical School, Rheinische Friedrich-Wilhelms University of Bonn, 53121 Bonn, Germany

5Department of Surgical Research, BG University Hospital Bergmannsheil, 44789 Bochum, Germany

6Department of Neurosurgery, University Hospital of Marburg, 35033 Marburg, Germany

*These authors contributed equally to this work

Correspondence to:

Konstantinos Gousias, email: [email protected]

Keywords: glioblastoma multiforme; karyopherin a2; U87 MG; nucleocytoplasmic transport

Received: December 13, 2017     Accepted: August 04, 2018     Published: September 11, 2018


We have previously shown that the nucleocytoplasmic carrier karyopherin a2 (KPNA2) is overexpressed in glioblastoma multiforme (GBM) whereas its expression is inversely associated with patient prognosis. However, the promoting role of KPNA2 in gliomagenesis is still poorly understood. This study aims to further elucidate this role of KPNA2 in in vitro GBM models.

From four different tested GBM cell lines, the U87MG showed the highest proliferation, low adherence and outgrowth in 3D clusters as well as the highest expression of KPNA2, all features conferring greater malignant behaviour. Silencing of KPNA2 via siRNA interference in those cells significantly decreased their proliferative capacity (p = 0.001). We further observed both a significant cell cycle phase arrest (p = 0.040) and the promoting of cellular apoptosis (p = 0.016) as well as a strong trend (p = 0.062) for an inhibition of nuclear import of c-Myc.

This study confirms that a higher expression of KPNA2 in GBM is associated with a more malignant phenotype also in in vitro models. While increased expression of KPNA2 promotes proliferation and survival of GBM tumour cells, silencing of KPNA2 conferred a less malignant behaviour. Our results strongly suggest that silencing of KPNA2 may play an important role in modulation of malignant features of GBM cells.

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