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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...

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Autores principales: Ma, Renqiang, Wei, Yi, Huang, Xiaoming, Fu, Ran, Luo, Xi, Zhu, Xiaolin, Lei, Wenbin, Fang, Jugao, Li, Huabin, Wen, Weiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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.
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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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