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Updated: Mar 13, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Notch3 negatively regulates chemoresistance in breast cancers

Xiaoting Gu1, Chunxiao Lu1, Dongxu He2

  • 1School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu, 214122, China.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|October 16, 2016
PubMed

Insights

The Notch3-Fra1 pathway drives chemoresistance and epithelial-mesenchymal transition (EMT) in breast cancer. Restoring Notch3 combats adriamycin resistance and EMT, indicating therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Chemoresistance is a major challenge in breast cancer treatment.
  • The epithelial-mesenchymal transition (EMT) is linked to chemoresistance and metastasis.
  • The role of the NOTCH signaling pathway in chemoresistance and EMT requires further elucidation.

Purpose of the Study:

  • To investigate the role of Notch3 in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM).
  • To determine the relationship between Notch3, fos-related antigen 1 (Fra1), and EMT in chemoresistance.
  • To assess Notch3 expression in clinical breast cancer samples and its prognostic value.

Main Methods:

  • Utilized adriamycin-resistant human breast cancer cell lines (MCF-7/ADM).
  • Investigated Notch3 expression and function through forced expression studies.
  • Assessed the regulation of Fra1 by Notch3 and its impact on EMT.
  • Analyzed Notch3 expression in patient-derived chemoresistant breast cancer samples.

Main Results:

  • Notch3 was downregulated in MCF-7/ADM cells and its forced expression reversed chemoresistance.
  • Fra1 was negatively regulated by Notch3, highly expressed in resistant cells, and activated EMT.
  • Low Notch3 expression correlated with unfavorable distant relapse-free survival in ER-positive breast cancers.

Conclusions:

  • The Notch3-Fra1 signaling pathway mediates chemoresistance through EMT in breast cancer.
  • Notch3 downregulation is implicated in chemoresistance development.
  • Notch3 expression serves as a prognostic marker for relapse in ER-positive breast cancer.
Keywords:
Breast cancerChemoresistanceEMTFra1Notch3

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