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Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma
BACKGROUND: Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715493/ https://www.ncbi.nlm.nih.gov/pubmed/23874688 http://dx.doi.org/10.1371/journal.pone.0068614 |
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author | Ma, Renqiang Wei, Yi Huang, Xiaoming Fu, Ran Luo, Xi Zhu, Xiaolin Lei, Wenbin Fang, Jugao Li, Huabin Wen, Weiping |
author_facet | Ma, Renqiang Wei, Yi Huang, Xiaoming Fu, Ran Luo, Xi Zhu, Xiaolin Lei, Wenbin Fang, Jugao Li, Huabin Wen, Weiping |
author_sort | Ma, Renqiang |
collection | PubMed |
description | BACKGROUND: Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3β) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3β, it is possible that inactivation of GSK3β may lead to excessive EZH2 expression in NPC. METHOD: We first examined the expression of EZH2 and phosphorylated GSK3β (p-GSK3β) by immunohistochemical staining in NPC samples. Then, we evaluated the interaction of GSK3β and EZH2 using immunoprecipitation and immune blot. Moreover, we determined the effect of inhibition of GSK3β activity on EZH2 expression and tumor invasiveness in NPC cell lines in vitro. Finally, we evaluated the invasive properties of NPC cells after knocking down EZH2 expression with EZH2 siRNA. RESULTS: We found that expression of EZH2 correlated with phosphorylated GSK3β (p-GSK3β) at Ser 9 (an inactivated form of GSK3β) in human nasopharyngeal carcinoma (NPC) samples. We also provided evidence that GSK3β is able to interact with EZH2 using immunoprecipitation and immune blot. Furthermore, we found that inhibition of GSK3β activity can lead to upregulation of EZH2 in NPC cell lines in vitro, with enhanced local invasiveness. By knocking down EZH2 expression with EZH2 siRNA, we found that these invasive properties were EZH2 dependent. CONCLUSION: Our findings indicate that GSK3β inactivation may account for EZH2 overexpression and subsequent tumour progression, and this mechanism might be a potential target for NPC therapy. |
format | Online Article Text |
id | pubmed-3715493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37154932013-07-19 Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma Ma, Renqiang Wei, Yi Huang, Xiaoming Fu, Ran Luo, Xi Zhu, Xiaolin Lei, Wenbin Fang, Jugao Li, Huabin Wen, Weiping PLoS One Research Article BACKGROUND: Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3β) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3β, it is possible that inactivation of GSK3β may lead to excessive EZH2 expression in NPC. METHOD: We first examined the expression of EZH2 and phosphorylated GSK3β (p-GSK3β) by immunohistochemical staining in NPC samples. Then, we evaluated the interaction of GSK3β and EZH2 using immunoprecipitation and immune blot. Moreover, we determined the effect of inhibition of GSK3β activity on EZH2 expression and tumor invasiveness in NPC cell lines in vitro. Finally, we evaluated the invasive properties of NPC cells after knocking down EZH2 expression with EZH2 siRNA. RESULTS: We found that expression of EZH2 correlated with phosphorylated GSK3β (p-GSK3β) at Ser 9 (an inactivated form of GSK3β) in human nasopharyngeal carcinoma (NPC) samples. We also provided evidence that GSK3β is able to interact with EZH2 using immunoprecipitation and immune blot. Furthermore, we found that inhibition of GSK3β activity can lead to upregulation of EZH2 in NPC cell lines in vitro, with enhanced local invasiveness. By knocking down EZH2 expression with EZH2 siRNA, we found that these invasive properties were EZH2 dependent. CONCLUSION: Our findings indicate that GSK3β inactivation may account for EZH2 overexpression and subsequent tumour progression, and this mechanism might be a potential target for NPC therapy. Public Library of Science 2013-07-18 /pmc/articles/PMC3715493/ /pubmed/23874688 http://dx.doi.org/10.1371/journal.pone.0068614 Text en © 2013 Ma et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ma, Renqiang Wei, Yi Huang, Xiaoming Fu, Ran Luo, Xi Zhu, Xiaolin Lei, Wenbin Fang, Jugao Li, Huabin Wen, Weiping Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma |
title | Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma |
title_full | Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma |
title_fullStr | Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma |
title_full_unstemmed | Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma |
title_short | Inhibition of GSK 3β Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma |
title_sort | inhibition of gsk 3β activity is associated with excessive ezh2 expression and enhanced tumour invasion in nasopharyngeal carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715493/ https://www.ncbi.nlm.nih.gov/pubmed/23874688 http://dx.doi.org/10.1371/journal.pone.0068614 |
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