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

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 inhibi...

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Autores principales: Carden, Sarah, van der Watt, Pauline, Chi, Alicia, Ajayi-Smith, Aderonke, Hadley, Katie, Leaner, Virna D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240311/
https://www.ncbi.nlm.nih.gov/pubmed/30445944
http://dx.doi.org/10.1186/s12885-018-5044-8
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author Carden, Sarah
van der Watt, Pauline
Chi, Alicia
Ajayi-Smith, Aderonke
Hadley, Katie
Leaner, Virna D.
author_facet Carden, Sarah
van der Watt, Pauline
Chi, Alicia
Ajayi-Smith, Aderonke
Hadley, Katie
Leaner, Virna D.
author_sort Carden, Sarah
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5044-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-62403112018-11-23 A tight balance of Karyopherin β1 expression is required in cervical cancer cells Carden, Sarah van der Watt, Pauline Chi, Alicia Ajayi-Smith, Aderonke Hadley, Katie Leaner, Virna D. BMC Cancer Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5044-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-16 /pmc/articles/PMC6240311/ /pubmed/30445944 http://dx.doi.org/10.1186/s12885-018-5044-8 Text en © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Carden, Sarah
van der Watt, Pauline
Chi, Alicia
Ajayi-Smith, Aderonke
Hadley, Katie
Leaner, Virna D.
A tight balance of Karyopherin β1 expression is required in cervical cancer cells
title A tight balance of Karyopherin β1 expression is required in cervical cancer cells
title_full A tight balance of Karyopherin β1 expression is required in cervical cancer cells
title_fullStr A tight balance of Karyopherin β1 expression is required in cervical cancer cells
title_full_unstemmed A tight balance of Karyopherin β1 expression is required in cervical cancer cells
title_short A tight balance of Karyopherin β1 expression is required in cervical cancer cells
title_sort tight balance of karyopherin β1 expression is required in cervical cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240311/
https://www.ncbi.nlm.nih.gov/pubmed/30445944
http://dx.doi.org/10.1186/s12885-018-5044-8
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