Cargando…
Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells
PURPOSE: Chromosomal instability (CIN) contributes to intercellular genetic heterogeneity and has been implicated in paclitaxel (PTX) resistance in breast cancer. In this study, we explored polo-like kinase 1 (PLK1) as an important regulator of mitotic integrity and as a useful predictive biomarker...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Breast Cancer Society
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250878/ https://www.ncbi.nlm.nih.gov/pubmed/35775700 http://dx.doi.org/10.4048/jbc.2022.25.e28 |
_version_ | 1784739904225280000 |
---|---|
author | Quan, Mingji Oh, Yumi Cho, Sung-Yup Kim, Ju Hee Moon, Hyeong-Gon |
author_facet | Quan, Mingji Oh, Yumi Cho, Sung-Yup Kim, Ju Hee Moon, Hyeong-Gon |
author_sort | Quan, Mingji |
collection | PubMed |
description | PURPOSE: Chromosomal instability (CIN) contributes to intercellular genetic heterogeneity and has been implicated in paclitaxel (PTX) resistance in breast cancer. In this study, we explored polo-like kinase 1 (PLK1) as an important regulator of mitotic integrity and as a useful predictive biomarker for PTX resistance in breast cancer. METHODS: We performed PTX resistance screening using the human kinome CRISPR/Cas9 library in breast cancer cells. In vitro cell proliferation and apoptosis assays and in vivo xenograft experiments were performed to determine the effects of PLK1 on breast cancer cells. Immunofluorescence microscopy was used to measure the degree of multipolar cell division. RESULTS: Kinome-wide CRISPR/Cas9 screening identified various kinases involved in PTX resistance in breast cancer cells; among these, PLK1 was chosen for further experiments. PLK1 knockdown inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells in vitro and in vivo. Moreover, PLK1 silencing sensitized breast cancer cells and mouse xenograft tumor models to PTX cytotoxicity. Silencing of PLK1 induced the formation of multipolar spindles and increased the percentage of multipolar cells. In addition, PLK1 silencing resulted in the downregulation of BubR1 and Mad2 in breast cancer cells. Furthermore, PLK1 upregulation in primary breast cancer was associated with decreased overall patient survival based on the analysis of The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium databases. CONCLUSION: PLK1 plays an important role in PTX resistance by regulating CIN in breast cancer cells. Targeting PLK1 may be an effective treatment strategy for PTX-resistant breast cancers. |
format | Online Article Text |
id | pubmed-9250878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Korean Breast Cancer Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-92508782022-07-06 Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells Quan, Mingji Oh, Yumi Cho, Sung-Yup Kim, Ju Hee Moon, Hyeong-Gon J Breast Cancer Original Article PURPOSE: Chromosomal instability (CIN) contributes to intercellular genetic heterogeneity and has been implicated in paclitaxel (PTX) resistance in breast cancer. In this study, we explored polo-like kinase 1 (PLK1) as an important regulator of mitotic integrity and as a useful predictive biomarker for PTX resistance in breast cancer. METHODS: We performed PTX resistance screening using the human kinome CRISPR/Cas9 library in breast cancer cells. In vitro cell proliferation and apoptosis assays and in vivo xenograft experiments were performed to determine the effects of PLK1 on breast cancer cells. Immunofluorescence microscopy was used to measure the degree of multipolar cell division. RESULTS: Kinome-wide CRISPR/Cas9 screening identified various kinases involved in PTX resistance in breast cancer cells; among these, PLK1 was chosen for further experiments. PLK1 knockdown inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells in vitro and in vivo. Moreover, PLK1 silencing sensitized breast cancer cells and mouse xenograft tumor models to PTX cytotoxicity. Silencing of PLK1 induced the formation of multipolar spindles and increased the percentage of multipolar cells. In addition, PLK1 silencing resulted in the downregulation of BubR1 and Mad2 in breast cancer cells. Furthermore, PLK1 upregulation in primary breast cancer was associated with decreased overall patient survival based on the analysis of The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium databases. CONCLUSION: PLK1 plays an important role in PTX resistance by regulating CIN in breast cancer cells. Targeting PLK1 may be an effective treatment strategy for PTX-resistant breast cancers. Korean Breast Cancer Society 2022-06-16 /pmc/articles/PMC9250878/ /pubmed/35775700 http://dx.doi.org/10.4048/jbc.2022.25.e28 Text en © 2022 Korean Breast Cancer Society https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Quan, Mingji Oh, Yumi Cho, Sung-Yup Kim, Ju Hee Moon, Hyeong-Gon Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells |
title | Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells |
title_full | Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells |
title_fullStr | Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells |
title_full_unstemmed | Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells |
title_short | Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells |
title_sort | polo-like kinase 1 regulates chromosomal instability and paclitaxel resistance in breast cancer cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250878/ https://www.ncbi.nlm.nih.gov/pubmed/35775700 http://dx.doi.org/10.4048/jbc.2022.25.e28 |
work_keys_str_mv | AT quanmingji pololikekinase1regulateschromosomalinstabilityandpaclitaxelresistanceinbreastcancercells AT ohyumi pololikekinase1regulateschromosomalinstabilityandpaclitaxelresistanceinbreastcancercells AT chosungyup pololikekinase1regulateschromosomalinstabilityandpaclitaxelresistanceinbreastcancercells AT kimjuhee pololikekinase1regulateschromosomalinstabilityandpaclitaxelresistanceinbreastcancercells AT moonhyeonggon pololikekinase1regulateschromosomalinstabilityandpaclitaxelresistanceinbreastcancercells |