A tight balance of Karyopherin β1 expression is required in cervical cancer cells

 

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dc.contributor.author Carden, Sarah
dc.contributor.author van der Watt, Pauline
dc.contributor.author Chi, Alicia
dc.contributor.author Ajayi-Smith, Aderonke
dc.contributor.author Hadley, Katie
dc.contributor.author Leaner, Virna D
dc.date.accessioned 2018-11-20T09:56:19Z
dc.date.available 2018-11-20T09:56:19Z
dc.date.issued 2018-11-16
dc.identifier.citation BMC Cancer. 2018 Nov 16;18(1):1123
dc.identifier.uri https://doi.org/10.1186/s12885-018-5044-8
dc.identifier.uri http://hdl.handle.net/11427/29068
dc.description.abstract Background Karyopherin β1 (Kpnβ1) is the main nuclear import protein involved in the transport of cargoes from the cytoplasm into the cell nucleus. Previous research has found Kpnβ1 to be significantly overexpressed in cervical cancer and other cancer tissues, and further studies showed that inhibition of Kpnβ1 expression by siRNA resulted in cancer cell death, while non-cancer cells were minimally affected. These results suggest that Kpnβ1 has potential as an anticancer therapeutic target, thus warranting further research into the association between Kpnβ1 expression and cancer progression. Here, the biological effects associated with Kpnβ1 overexpression were investigated in order to further elucidate the relationship between Kpnβ1 and the cancer phenotype. Methods To evaluate the effect of Kpnβ1 overexpression on cell biology, cell proliferation, cell cycle, cell morphology and cell adhesion assays were performed. To determine whether Kpnβ1 overexpression influences cell sensitivity to chemotherapeutic agents like Cisplatin, cell viability assays were performed. Expression levels of key proteins were analysed by Western blot analysis. Results Our data revealed that Kpnβ1 overexpression, above that which was already detected in cancer cells, resulted in reduced proliferation of cervical cancer cells. Likewise, normal epithelial cells showed reduced proliferation after Kpnβ1 overxpression. Reduced cancer cell proliferation was associated with a delay in cell cycle progression, as well as changes in the morphology and adhesion properties of cells. Additionally, Kpnβ1 overexpressing HeLa cells exhibited increased sensitivity to cisplatin, as shown by decreased cell viability and increased apoptosis, where p53 and p21 inhibition reduced and enhanced cell sensitivity to Cisplatin, respectively. Conclusions Overall, our results suggest that a tight balance of Kpnβ1 expression is required for cellular function, and that perturbation of this balance results in negative effects associated with a variety of biological processes.
dc.language.iso en
dc.publisher BioMed Central
dc.source BMC Cancer
dc.source.uri https://bmccancer.biomedcentral.com/
dc.subject.other Karypherin β1
dc.subject.other Overexpression
dc.subject.other Cancer biology
dc.title A tight balance of Karyopherin β1 expression is required in cervical cancer cells
dc.type Journal Article
dc.date.updated 2018-11-18T04:25:16Z
dc.rights.holder The Author(s).
dc.publisher.institution University of Cape Town
uct.type.filetype Text
uct.type.filetype Image


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