4.5 Article

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

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 10, Pages 6942-6954

Publisher

WILEY
DOI: 10.1111/jcmm.14579

Keywords

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

Funding

  1. National Natural Science Foundation of China [81502357, 81672672, 81572650, 81772891, 81621062]
  2. State Key Laboratory of Oral Diseases Special Funded Projects
  3. Zhoushan Science and Technology Bureau Project [2014C31068]
  4. Natural Science Foundation of Zhejiang Province [Q142114001]

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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.

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