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Updated: May 26, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch: a key regulator of tumor angiogenesis and metastasis
Alejandro Garcia1, Jessica J Kandel
1Division of Pediatric Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA. alg2025@columbia.edu
Abstract:
The Notch signaling pathway is critical for many developmental processes including physiologic angiogenesis. Notch is also implicated in having a key role in tumor angiogenesis. Preclinical and clinical experience with anti-angiogenic strategies indicates that they may be limited by tumor resistance and recurrence, which has led to the search for alternative angiogenic treatment strategies. Significant progress has been made in shedding light on the complex mechanisms by which Notch signaling can influence tumor growth by disrupting vasculature in an array of tumor models (Ridgway et al., 2006). These results have led to the consideration of Notch as an attractive target to block tumor angiogenesis and inhibit growth. However, studies of inhibition of Notch signaling in different tumor models have uncovered similarly variable results, and some unexpected adverse effects. The ability of Notch to function in a context-dependent manner as a determinant of cell fate, a tumor suppressor, and an oncogene may partially explain the complexity in interpreted the role of Notch signaling inhibitors in preclinical tumor studies. In addition, Notch may also play an important role in metastasis via its direct effects on the vasculature and by modulation of epithelial-mesenchymal transition in tumor cells. Here we present a current understanding of Notch signaling in tumor angiogenesis, and discuss recent work on the role of Notch in tumor metastatic progression.
Insights
The Notch signaling pathway influences tumor angiogenesis and metastasis. Inhibiting Notch shows variable results, highlighting its complex, context-dependent roles in cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Developmental Biology
Background:
- The Notch signaling pathway is crucial for physiological angiogenesis and is implicated in tumor angiogenesis.
- Anti-angiogenic therapies face challenges with tumor resistance and recurrence, necessitating alternative strategies.
- Notch signaling's complex role in tumor growth, vasculature disruption, and metastasis requires further elucidation.
Purpose of the Study:
- To review the current understanding of Notch signaling in tumor angiogenesis.
- To discuss the role of Notch signaling in tumor metastatic progression.
- To explore the context-dependent functions of Notch in cancer.
Main Methods:
- Literature review of preclinical and clinical studies on Notch signaling in cancer.
- Analysis of research on Notch's influence on tumor vasculature and epithelial-mesenchymal transition.
- Synthesis of findings regarding Notch inhibitors' efficacy and adverse effects.
Main Results:
- Notch signaling significantly impacts tumor angiogenesis and growth by affecting vasculature.
- Inhibition of Notch signaling yields variable results across different tumor models, with some adverse effects.
- Notch signaling plays a role in tumor metastasis through vascular effects and modulation of epithelial-mesenchymal transition.
Conclusions:
- Notch signaling is a complex regulator of tumor angiogenesis and metastasis.
- The context-dependent functions of Notch (cell fate determinant, tumor suppressor, oncogene) complicate therapeutic targeting.
- Further research is needed to fully understand and leverage Notch signaling for cancer treatment.
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