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BMC Cancer. 2018 Mar 27;18(1):325. doi: 10.1186/s12885-018-4261-5.

Depletion of nuclear import protein karyopherin alpha 7 (KPNA7) induces mitotic defects and deformation of nuclei in cancer cells.

Author information

1
BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.
2
BioMediTech Institute and Faculty of Biomedical Sciences and Engineering, Tampere University of Technology, University of Tampere, PL 100, 33014, Tampere, Finland.
3
Tampere Imaging Facility, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland.
4
BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, PL 100, 33014, Tampere, Finland. anne.kallioniemi@uta.fi.
5
Fimlab Laboratories, Biokatu 4, 33520, Tampere, Finland. anne.kallioniemi@uta.fi.

Abstract

BACKGROUND:

Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the karyopherin alpha nuclear importer family, is expressed at a high level during embryogenesis, reduced to very low or absent levels in most adult tissues but re-expressed in cancer cells.

METHODS:

We used siRNA-based knock-down of KPNA7 in cancer cell lines, followed by functional assays (proliferation and cell cycle) and immunofluorescent stainings to determine the role of KPNA7 in regulation of cancer cell growth, proper mitosis and nuclear morphology.

RESULTS:

In the present study, we show that the silencing of KPNA7 results in a dramatic reduction in pancreatic and breast cancer cell growth, irrespective of the endogenous KPNA7 expression level. This growth inhibition is accompanied by a decrease in the fraction of S-phase cells as well as aberrant number of centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7 depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina proteins, and drastic alterations in nuclear morphology with lobulated and elongated nuclei.

CONCLUSIONS:

Taken together, our data provide new important evidence on the contribution of KPNA7 to the regulation of cancer cell growth and the maintenance of nuclear envelope environment, and thus deepens our understanding on the impact of nuclear transfer proteins in cancer pathogenesis.

KEYWORDS:

Cell proliferation; Importin alpha 8; KPNA7; Mitosis; Nuclear morphology; Nuclear transfer

PMID:
29580221
PMCID:
PMC5870926
DOI:
10.1186/s12885-018-4261-5
[Indexed for MEDLINE]
Free PMC Article

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