%0 Journal Article
%T Inhibition of GSK 3¦Â Activity Is Associated with Excessive EZH2 Expression and Enhanced Tumour Invasion in Nasopharyngeal Carcinoma
%A Renqiang Ma
%A Yi Wei
%A Xiaoming Huang
%A Ran Fu
%A Xi Luo
%A Xiaolin Zhu
%A Wenbin Lei
%A Jugao Fang
%A Huabin Li
%A Weiping Wen
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0068614
%X 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 (GSK3¦Â) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3¦Â, it is possible that inactivation of GSK3¦Â may lead to excessive EZH2 expression in NPC. Method We first examined the expression of EZH2 and phosphorylated GSK3¦Â (p-GSK3¦Â) by immunohistochemical staining in NPC samples. Then, we evaluated the interaction of GSK3¦Â and EZH2 using immunoprecipitation and immune blot. Moreover, we determined the effect of inhibition of GSK3¦Â 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 GSK3¦Â (p-GSK3¦Â) at Ser 9 (an inactivated form of GSK3¦Â) in human nasopharyngeal carcinoma (NPC) samples. We also provided evidence that GSK3¦Â is able to interact with EZH2 using immunoprecipitation and immune blot. Furthermore, we found that inhibition of GSK3¦Â 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 GSK3¦Â inactivation may account for EZH2 overexpression and subsequent tumour progression, and this mechanism might be a potential target for NPC therapy.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0068614