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Updated: Aug 8, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer

Sonia Brahim1, Ana-Maria Negulescu1, Clara Geneste1

  • 1Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France.

Cell Death & Disease
|February 28, 2023
PubMed

Insights

Notch3 signaling acts as a tumor suppressor in breast cancer. Loss of Notch3 accelerates tumor growth by increasing cell cycle regulator Mybl2, reinforcing its protective role against breast tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Notch signaling is crucial for mammary gland development and homeostasis.
  • Notch signaling has been linked to breast tumorigenesis, but the specific role of Notch3 remains debated.

Purpose of the Study:

  • To investigate the role of Notch3 in breast cancer development.
  • To analyze Notch3 expression in human breast cancer samples and its prognostic value.
  • To determine the functional impact of Notch3 loss in a mouse model of breast cancer.

Main Methods:

  • Analysis of Notch3 expression in human breast cancer tissues.
  • Investigation of Notch3 function in a MMTV-Neu mouse model of breast cancer.
  • Assessment of Mybl2 (a cell cycle regulator) expression in Notch3-deficient tumors.

Main Results:

  • Notch3 expression was weak in breast cancer cells but strong in stromal cells, with weak expression correlating with good patient prognosis.
  • Loss of Notch3 in mice accelerated tumor initiation and proliferation.
  • Notch3-deficient tumors showed increased Mybl2 mRNA and protein expression, indicating Notch3's inhibitory role via HeyL-mediated Mybl2 suppression.

Conclusions:

  • Notch3 exhibits an anti-tumoral role in breast cancer, preventing tumor initiation.
  • Notch3 functions by inhibiting Mybl2, a key regulator of the cell cycle.
  • These findings reinforce the tumor-suppressive function of Notch3 in breast tumorigenesis.

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