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Open Access 01-12-2018 | Research

The polycomb group protein EZH2 induces epithelial–mesenchymal transition and pluripotent phenotype of gastric cancer cells by binding to PTEN promoter

Authors: Lu Gan, Midie Xu, Ruixi Hua, Cong Tan, Jieyun Zhang, Yiwei Gong, Zhenhua Wu, Weiwei Weng, Weiqi Sheng, Weijian Guo

Published in: Journal of Hematology & Oncology | Issue 1/2018

Abstract

Background

The influences of oncogenic Ezh2 on the progression and prognosis of gastric cancer (GC) and the underlying mechanisms are still poorly understood. Here, we aimed at investigating clinicopathological significance of Ezh2 in GC and the mechanisms underlying its function in GC development.

Methods

The expression level of Ezh2 was determined by qRT-PCR, immunoblot, and immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal gastric mucosa tissues. The biological functions of Ezh2 were assessed by in vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP), luciferase, and Western blotting analyses were utilized to identify the relationship between Ezh2 and the PTEN/Akt signaling.

Results

The expression of Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous epithelium. High expression of Ezh2 was associated with more aggressive biological behavior and poor prognosis in GC. In vitro studies indicated that Ezh2 promoted GC cells’ proliferation and clonogenicity. Besides, Ezh2 led to the acquisition of epithelial–mesenchymal transition (EMT) phenotype of GC cells and enhanced GC cell migration and invasion capacity. In particular, Ezh2 strengthened sphere-forming capacity of GC cells, indicating its role in the enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype in GC cells, and blocking PTEN signaling significantly rescued the effects of Ezh2.

Conclusions

Taken together, Ezh2 has a central role in regulating diverse aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling, indicating that it could be an independent prognostic factor and potential therapeutic target.

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Title: The polycomb group protein EZH2 induces epithelial–mesenchymal transition and pluripotent phenotype of gastric cancer cells by binding to PTEN promoter
Authors: Lu Gan
Midie Xu
Ruixi Hua
Cong Tan
Jieyun Zhang
Yiwei Gong
Zhenhua Wu
Weiwei Weng
Weiqi Sheng
Weijian Guo
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-017-0547-3

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