Related Experiment Video

Updated: Jan 30, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
11:34

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

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EZH2 directs HER2+ breast cancer progression through the modulation of epithelial plasticity

Linshan Liu1,2, Ellie J Massey1,2, Dongmei Zuo2

  • 1Department of Biochemistry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.

EMBO Reports
|January 28, 2026
PubMed

Insights

Enhancer of Zeste Homolog 2 (EZH2) drives aggressive HER2+ breast cancer progression and metastasis. Inhibiting EZH2 increases estrogen receptor expression, making tumors sensitive to endocrine therapies like Tamoxifen.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • HER2-positive (HER2+) breast cancer is aggressive and develops resistance to targeted therapies.
  • Enhancer of Zeste Homolog 2 (EZH2) regulates gene expression critical for cell function.
  • EZH2's role in HER2+ breast cancer progression and therapy resistance is not fully understood.

Purpose of the Study:

  • To investigate the role of EZH2 in HER2+ breast cancer initiation and metastasis.
  • To determine how EZH2 influences cellular plasticity and gene expression in HER2+ tumors.
  • To evaluate the therapeutic potential of combining EZH2 inhibition with endocrine therapy.

Main Methods:

  • Utilized a genetically engineered mouse model of HER2+ breast cancer with conditional Ezh2 knockout.
  • Performed bulk and single-cell RNA sequencing to analyze gene expression changes.
  • Investigated EZH2 inhibition effects on HER2+ human breast cancer cell lines in vitro.

Main Results:

  • Ezh2 deficiency accelerated tumor initiation and metastatic dissemination in mice.
  • Loss of Ezh2 led to decreased basal cell populations and increased luminal progenitor populations, involving Esr1.
  • In vitro EZH2 inhibition increased estrogen receptor (ER) expression and tamoxifen sensitivity in HER2+ cells.

Conclusions:

  • EZH2 plays a critical role in driving cancer cell plasticity in HER2+ breast cancer.
  • Targeting EZH2 may overcome resistance to HER2-targeted therapies.
  • Combining EZH2 inhibitors with endocrine therapies offers a promising strategy to improve treatment outcomes for HER2+ breast cancer.
Keywords:
Breast CancerEZH2EpigeneticsEstrogen ReceptorPlasticity

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