EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells

J Cell Mol Med. 2019 Oct;23(10):6942-6954. doi: 10.1111/jcmm.14579. Epub 2019 Jul 31.

Abstract

The enhancer of zeste homolog 2 (EZH2), known as a member of the polycomb group (PcG) proteins, is an oncogene overexpressed in a variety of human cancers. Here, we found that EZH2 correlated with poor survival of oral squamous cell carcinoma (OSCC) patients using immunohistochemistry staining. EZH2 overexpression led to a significant induction in tumour glycolysis, Epithelial-mesenchymal transition (EMT), migration and invasion of OSCC cells. Conversely, silencing of EZH2 inhibited tumour glycolysis, EMT, migration and invasion in OSCC cells. Ectopic overexpression of EZH2 increased phosphorylation of STAT3 at pY705 and decreased FoxO1 expression, and FoxO1 expression was enhanced when inhibiting STAT3. In addition, EZH2 overexpression led to a significant decrease in FoxO1 mRNA levels in nude mice xenograft. These results indicated that regulation of EZH2 might have the potential to be targeted for OSCC treatment.

Keywords: FoxO1; STAT3; enhancer of zeste homolog 2; epithelial-mesenchymal transition; invasion; oral squamous cell carcinoma; tumour glycolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Down-Regulation / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glycolysis*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Phosphorylation
  • Prognosis
  • Proportional Hazards Models
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*
  • Survival Analysis

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein