A tight balance of Karyopherin β1 expression is required in cervical cancer cells
| 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.date.updated | 2018-11-18T04:25:16Z | |
| 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.identifier.apacitation | Carden, S., van der Watt, P., Chi, A., Ajayi-Smith, A., Hadley, K., & Leaner, V. D. (2018). A tight balance of Karyopherin β1 expression is required in cervical cancer cells. <i>BMC Cancer</i>, http://hdl.handle.net/11427/29068 | en_ZA |
| dc.identifier.chicagocitation | Carden, Sarah, Pauline van der Watt, Alicia Chi, Aderonke Ajayi-Smith, Katie Hadley, and Virna D Leaner "A tight balance of Karyopherin β1 expression is required in cervical cancer cells." <i>BMC Cancer</i> (2018) http://hdl.handle.net/11427/29068 | en_ZA |
| dc.identifier.citation | BMC Cancer. 2018 Nov 16;18(1):1123 | |
| dc.identifier.ris | TY - Journal Article AU - Carden, Sarah AU - van der Watt, Pauline AU - Chi, Alicia AU - Ajayi-Smith, Aderonke AU - Hadley, Katie AU - Leaner, Virna D AB - 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. DA - 2018-11-16 DB - OpenUCT DP - University of Cape Town J1 - BMC Cancer LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - A tight balance of Karyopherin β1 expression is required in cervical cancer cells TI - A tight balance of Karyopherin β1 expression is required in cervical cancer cells UR - http://hdl.handle.net/11427/29068 ER - | en_ZA |
| dc.identifier.uri | https://doi.org/10.1186/s12885-018-5044-8 | |
| dc.identifier.uri | http://hdl.handle.net/11427/29068 | |
| dc.identifier.vancouvercitation | Carden S, van der Watt P, Chi A, Ajayi-Smith A, Hadley K, Leaner VD. A tight balance of Karyopherin β1 expression is required in cervical cancer cells. BMC Cancer. 2018; http://hdl.handle.net/11427/29068. | en_ZA |
| dc.language.iso | en | |
| dc.publisher | BioMed Central | |
| dc.publisher.institution | University of Cape Town | |
| dc.rights.holder | The Author(s). | |
| 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 | |
| uct.type.filetype | Text | |
| uct.type.filetype | Image |