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Updated: Feb 26, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Published on: January 12, 2020

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Non-canonical NOTCH3 signalling limits tumour angiogenesis

Shuheng Lin1, Ana Negulescu1, Sirisha Bulusu1

  • 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.

Nature Communications
|July 19, 2017
PubMed

Insights

Notch3 promotes cancer cell death and inhibits tumor growth by triggering endothelial cell apoptosis. Jagged-1 blocks this effect, revealing a new therapeutic target for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Notch signalling is a key driver of cancer, with targeted therapies focusing on the canonical pathway.
  • The role of Notch3 in tumour angiogenesis and its interaction with ligands like Jagged-1 is not fully understood.

Purpose of the Study:

  • To investigate the non-canonical role of Notch3 in regulating tumour angiogenesis.
  • To elucidate the mechanism by which Jagged-1 influences Notch3-mediated endothelial cell apoptosis.
  • To assess the therapeutic implications of targeting Notch3 in cancer.

Main Methods:

  • Utilized Notch3 mutant mice to study tumour growth and angiogenesis.
  • Investigated the interaction between Notch3 and its ligand Jagged-1 in cancer models.
  • Analyzed the effect of γ-secretase inhibition on tumour vasculature and endothelial cell apoptosis.

Main Results:

  • Notch3 exhibits a pro-apoptotic role in tumour vasculature, independent of the canonical Notch pathway.
  • Cancer-derived Jagged-1 inhibits Notch3-induced endothelial cell death, promoting tumour growth and angiogenesis.
  • Tumour growth and angiogenesis are increased in Notch3-silenced mice.
  • The anti-tumour effects of γ-secretase inhibitors are partly mediated by Notch3-induced endothelial cell apoptosis.

Conclusions:

  • Notch3 acts as a dependence receptor, inducing endothelial cell death, a process inhibited by Jagged-1.
  • Targeting the Notch3-Jagged-1 interaction presents a novel therapeutic strategy for cancer.
  • Understanding this non-canonical Notch3 function is crucial for developing effective cancer therapies.

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