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Updated: Nov 21, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis
Julia O Misiorek1, Alicja Przybyszewska-Podstawka2, Joanna Kałafut2
1Department of Molecular Neurooncology, Institute of Bioorganic Chemistry Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704 Poznan, Poland.
Abstract:
The Notch signaling pathway is a critical player in embryogenesis but also plays various roles in tumorigenesis, with both tumor suppressor and oncogenic activities. Mutations, deletions, amplifications, or over-expression of Notch receptors, ligands, and a growing list of downstream Notch-activated genes have by now been described for most human cancer types. Yet, it often remains unclear what may be the functional impact of these changes for tumor biology, initiation, and progression, for cancer therapy, and for personalized medicine. Emerging data indicate that Notch signaling can also contribute to increased aggressive properties such as invasion, tumor heterogeneity, angiogenesis, or tumor cell dormancy within solid cancer tissues; especially in epithelial cancers, which are in the center of this review. Notch further supports the "stemness" of cancer cells and helps define the stem cell niche for their long-term survival, by integrating the interaction between cancer cells and the cells of the tumor microenvironment (TME). The complexity of Notch crosstalk with other signaling pathways and its roles in cell fate and trans-differentiation processes such as epithelial-to-mesenchymal transition (EMT) point to this pathway as a decisive player that may tip the balance between tumor suppression and promotion, differentiation and invasion. Here we not only review the literature, but also explore genomic databases with a specific focus on Notch signatures, and how they relate to different stages in tumor development. Altered Notch signaling hereby plays a key role for tumor cell survival and coping with a broad spectrum of vital issues, contributing to failed therapies, poor patient outcome, and loss of lives.
Insights
The Notch signaling pathway influences cancer development and progression. Understanding its complex roles in tumor biology is crucial for developing effective cancer therapies and improving patient outcomes.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- The Notch signaling pathway is essential for embryonic development and implicated in various cancers, exhibiting both tumor-suppressive and oncogenic functions.
- Alterations in Notch pathway components (receptors, ligands, downstream genes) are frequent across human cancers, but their functional impact on tumor biology and therapy remains incompletely understood.
- Emerging evidence highlights Notch signaling's role in promoting aggressive cancer phenotypes, including invasion, heterogeneity, angiogenesis, and cancer stem cell survival within the tumor microenvironment (TME).
Purpose of the Study:
- To review the multifaceted roles of Notch signaling in tumorigenesis, focusing on epithelial cancers.
- To explore the functional consequences of altered Notch signaling on tumor initiation, progression, and therapeutic response.
- To investigate Notch signatures in genomic databases and their correlation with tumor development stages.
Main Methods:
- Comprehensive literature review of Notch signaling in cancer.
- Exploration of genomic databases to identify and analyze Notch signatures.
- Correlation analysis of Notch signatures with different stages of tumor development.
Main Results:
- Notch signaling contributes to aggressive cancer traits like invasion, heterogeneity, angiogenesis, and stemness.
- The pathway integrates cancer cell interactions within the TME and influences cell fate decisions, including epithelial-to-mesenchymal transition (EMT).
- Altered Notch signaling is linked to therapeutic failure and poor patient prognosis.
Conclusions:
- The Notch pathway is a pivotal regulator in cancer, capable of promoting tumor suppression or progression.
- Its complex crosstalk with other pathways and role in cell plasticity make it a critical determinant of tumor behavior.
- Understanding Notch signatures is vital for deciphering its impact on tumor survival, treatment response, and patient outcomes.
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