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Updated: Jul 17, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch3/4 Knockdown Inhibits Colon Adenocarcinoma Progression by Suppressing Tumor Cell Activity and Orchestrating
Wei Liu1, Guhang Tang1, Ningfu Li1
1Department of Oncology, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing, China.
Background:
Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignancy characterized by dysregulation of multiple cellular signaling pathways, including the Notch pathway. However, the specific biological roles of Notch3 and Notch4 in COAD remain incompletely characterized.
Methods:
We aimed to investigate the effects of Notch3 and Notch4 downregulation on the tumor immune microenvironment and angiogenesis in COAD. Using a combination of in vitro and in vivo models, we evaluated the impacts of Notch3/4 interference on cell proliferation, migration, immune cell infiltration, and tumor progression.
Results:
Interfering with Notch3 and 4 significantly suppressed subcutaneous tumor progression. Notably, this inhibition was not only associated with reduced cell viability, but also with an altered immune environment characterized by enhanced macrophage M1 polarization and T lymphocyte activation, which may be linked to the c-Myc/VEGFA signaling axis but requires further mechanistic validation. Furthermore, the combination of regorafenib and Notch3/4 knockout (KO) exerted enhanced anti-tumor effects. More importantly, Mol_2, a candidate compound with predicted binding affinity for both Notch3 and Notch4, was screened out to significantly reduce the protein levels of Notch3 and Notch4 and tumor progression.
Conclusions:
Our findings suggest that targeting Notch3 and Notch4 receptors may have therapeutic potential for modulating the tumor microenvironment and suppressing tumor progression in COAD.
Insights
Targeting Notch3 and Notch4 receptors suppressed colon adenocarcinoma (COAD) progression by altering the tumor immune microenvironment. A novel compound, Mol_2, also showed significant anti-tumor effects in COAD models.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Colon adenocarcinoma (COAD) is a common cancer with poorly understood Notch pathway roles.
- Notch3 and Notch4 signaling in COAD pathogenesis require further elucidation.
Purpose of the Study:
- Investigate Notch3 and Notch4 downregulation effects on COAD's tumor immune microenvironment and angiogenesis.
- Evaluate impacts on cell proliferation, migration, immune cell infiltration, and tumor progression.
Main Methods:
- Utilized in vitro and in vivo COAD models.
- Assessed effects of Notch3/4 interference on tumor progression and immune cell activity.
- Screened for compounds targeting Notch3 and Notch4.
Main Results:
- Notch3/4 downregulation suppressed tumor progression, reduced cell viability, and enhanced M1 macrophage and T lymphocyte activity.
- Combined regorafenib and Notch3/4 knockout showed synergistic anti-tumor effects.
- Compound Mol_2 significantly reduced Notch3/4 protein levels and COAD tumor progression.
Conclusions:
- Targeting Notch3 and Notch4 receptors shows therapeutic potential for COAD.
- Modulating the tumor microenvironment via Notch3/4 inhibition may suppress COAD progression.
- Mol_2 represents a promising therapeutic candidate for COAD treatment.
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