Related Experiment Video

Updated: Sep 14, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
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Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

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Aberrant EZHIP expression drives tumorigenesis in osteosarcoma

Wajih Jawhar1,2,3, Geoffroy Danieau2,4, Alva Annett5,6

  • 1Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.

Nature Communications
|July 22, 2025
PubMed

Insights

EZHIP, a protein mimicking oncohistones, is frequently found in osteosarcomas (OS). Its expression predicts poor treatment response and drives tumor aggression by altering epigenetic marks and hindering cell differentiation.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Osteosarcomas (OS) are aggressive bone cancers with complex genetic alterations.
  • Recurrent oncogenic driver mutations are rare in OS, necessitating the identification of alternative pathogenic mechanisms.

Purpose of the Study:

  • To investigate the role of EZHIP (enhancer of zeste homolog 2-interacting protein) in osteosarcoma pathogenesis.
  • To determine if EZHIP expression correlates with patient outcomes and response to therapy.

Main Methods:

  • Analysis of EZHIP expression in two independent osteosarcoma patient cohorts.
  • Gain- and loss-of-function experiments to assess EZHIP's oncogenic activity in vitro and in vivo.
  • Evaluation of H3K27me3 deposition and its correlation with therapeutic response and patient prognosis.

Main Results:

  • Ectopic EZHIP expression was identified in 20% of osteosarcoma patients.
  • Reduced H3K27me3 levels, associated with EZHIP, correlated with poor histological response to neoadjuvant therapy and worse patient outcomes.
  • EZHIP promoted OS aggressiveness by reprogramming epigenetic marks, reactivating developmental pathways, and impairing mesenchymal progenitor differentiation towards non-smooth muscle lineages.

Conclusions:

  • EZHIP is a prevalent driver in osteosarcomas, contributing to tumor aggression and poor prognosis.
  • EZHIP-mediated epigenetic alterations impede normal cell differentiation, favoring a more aggressive tumor phenotype.
  • Targeting EZH2 in EZHIP-expressing osteosarcomas may represent a potential therapeutic strategy.

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