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Updated: May 17, 2025

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
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NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer

Pavla Ticha1,2, Jason J Northey1, Kelly Kersten3,4

  • 1Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA 94143, USA.

Biorxiv : the Preprint Server for Biology
|March 31, 2025
PubMed

Insights

Nuclear corepressor 2 (NCOR2) epigenetically regulates MHC class I expression in breast cancer. Reducing NCOR2 can enhance anti-tumor immunity and suppress metastasis, offering a potential therapeutic target for triple-negative breast cancer.

Area of Science:

  • Immunology
  • Epigenetics
  • Oncology

Background:

  • Metastasis relies on tumor cells evading immune surveillance.
  • MHC class I expression is crucial for T cell recognition and tumor cell eradication.

Purpose of the Study:

  • To identify key epigenetic regulators of MHC class I expression in breast cancer.
  • To investigate the role of nuclear corepressor 2 (NCOR2) in breast cancer metastasis and immune evasion.

Main Methods:

  • Analysis of NCOR2 expression in triple-negative breast cancer (TNBC) patient samples.
  • Genetic and experimental reduction of NCOR2 in tumor cells.
  • Assessment of MHC class I expression, CD8 T cell activity, and apoptosis induction.

Main Results:

  • High NCOR2 levels correlated with reduced metastasis-free survival and decreased MHC class I expression in TNBC patients.
  • Metastatic TNBC lesions showed high nuclear NCOR2 and reduced CD8 T cell activity.
  • Reducing NCOR2 expression restored interferon-gamma-induced MHC class I upregulation and enhanced CD8 T cell-mediated tumor cell apoptosis.

Conclusions:

  • NCOR2 is a critical epigenetic regulator of MHC class I expression and immune evasion in breast cancer metastasis.
  • Targeting NCOR2 may represent a novel therapeutic strategy to enhance anti-tumor immunity and reduce mortality in TNBC.

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