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CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A

Several previous studies have demonstrated that cyclin-dependent kinase (CDK)-5 expression serves an important role in promoting the development of malignant tumours. We have previously reported that CDK5 suppresses gastric tumourigenesis. The aim of the present study was to investigate the mechanis...

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Autores principales: Lu, Jun, Lin, Jian-Xian, Zhang, Peng-Yang, Sun, Yu-Qin, Li, Ping, Xie, Jian-Wei, Wang, Jia-Bin, Chen, Qi-Yue, Cao, Long-Long, Lin, Yao, Huang, Chang-Ming, Zheng, Chao-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312987/
https://www.ncbi.nlm.nih.gov/pubmed/30431123
http://dx.doi.org/10.3892/or.2018.6860
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author Lu, Jun
Lin, Jian-Xian
Zhang, Peng-Yang
Sun, Yu-Qin
Li, Ping
Xie, Jian-Wei
Wang, Jia-Bin
Chen, Qi-Yue
Cao, Long-Long
Lin, Yao
Huang, Chang-Ming
Zheng, Chao-Hui
author_facet Lu, Jun
Lin, Jian-Xian
Zhang, Peng-Yang
Sun, Yu-Qin
Li, Ping
Xie, Jian-Wei
Wang, Jia-Bin
Chen, Qi-Yue
Cao, Long-Long
Lin, Yao
Huang, Chang-Ming
Zheng, Chao-Hui
author_sort Lu, Jun
collection PubMed
description Several previous studies have demonstrated that cyclin-dependent kinase (CDK)-5 expression serves an important role in promoting the development of malignant tumours. We have previously reported that CDK5 suppresses gastric tumourigenesis. The aim of the present study was to investigate the mechanistic basis of CDK5. The results of immunoprecipitation and western blot analysis demonstrated that CDK5 could interact with serine/threonine-protein phosphatase 2A (PP2A). The use of an inhibitor of PP2A in CDK5-overexpressing gastric cancer (GC) cell lines antagonized CDK5-mediated suppression in GC cells. Further analysis revealed that PP2A expression was downregulated in GC and patients with low levels of PP2A had worse survival outcomes than those with high levels of PP2A (P=0.035). Therefore, the present study provided a novel mechanism for CDK5-mediated tumour suppression, suggesting that CDK5 may be an attractive target for future therapeutic strategies for treating GC. In addition, low levels of PP2A may indicate a tendency for poor prognosis in patients with GC.
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spelling pubmed-63129872019-01-17 CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A Lu, Jun Lin, Jian-Xian Zhang, Peng-Yang Sun, Yu-Qin Li, Ping Xie, Jian-Wei Wang, Jia-Bin Chen, Qi-Yue Cao, Long-Long Lin, Yao Huang, Chang-Ming Zheng, Chao-Hui Oncol Rep Articles Several previous studies have demonstrated that cyclin-dependent kinase (CDK)-5 expression serves an important role in promoting the development of malignant tumours. We have previously reported that CDK5 suppresses gastric tumourigenesis. The aim of the present study was to investigate the mechanistic basis of CDK5. The results of immunoprecipitation and western blot analysis demonstrated that CDK5 could interact with serine/threonine-protein phosphatase 2A (PP2A). The use of an inhibitor of PP2A in CDK5-overexpressing gastric cancer (GC) cell lines antagonized CDK5-mediated suppression in GC cells. Further analysis revealed that PP2A expression was downregulated in GC and patients with low levels of PP2A had worse survival outcomes than those with high levels of PP2A (P=0.035). Therefore, the present study provided a novel mechanism for CDK5-mediated tumour suppression, suggesting that CDK5 may be an attractive target for future therapeutic strategies for treating GC. In addition, low levels of PP2A may indicate a tendency for poor prognosis in patients with GC. D.A. Spandidos 2019-02 2018-11-09 /pmc/articles/PMC6312987/ /pubmed/30431123 http://dx.doi.org/10.3892/or.2018.6860 Text en Copyright: © Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lu, Jun
Lin, Jian-Xian
Zhang, Peng-Yang
Sun, Yu-Qin
Li, Ping
Xie, Jian-Wei
Wang, Jia-Bin
Chen, Qi-Yue
Cao, Long-Long
Lin, Yao
Huang, Chang-Ming
Zheng, Chao-Hui
CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A
title CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A
title_full CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A
title_fullStr CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A
title_full_unstemmed CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A
title_short CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A
title_sort cdk5 suppresses the metastasis of gastric cancer cells by interacting with and regulating pp2a
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312987/
https://www.ncbi.nlm.nih.gov/pubmed/30431123
http://dx.doi.org/10.3892/or.2018.6860
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