ArticlePloS one2016
NOTCH3 Is Induced in Cancer-Associated Fibroblasts and Promotes Angiogenesis in Oral Squamous Cell Carcinoma.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancer.Science advances · 2026Article
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- Molecular remodeling of cancer-associated fibroblasts in breast cancer patients receiving anti-PD-1 immunotherapy.Frontiers in oncology · 2026Article
- Emerging role of cancer-associated fibroblasts in the premetastatic niche.Molecular cancer · 2025Review
- Exploring Cancer-Associated Fibroblasts in OSCC and OPMDs: Microenvironment Insights. Scoping Review.Oral diseases · 2025Article
- Tumor and α-SMA-expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade.Molecular oncology · 2025Article
- Fibroblast-immune crosstalk in oral squamous cell carcinoma: from tumor promotion to immune evasion.Frontiers in immunology · 2025Review
- Crosstalk between CAFs and tumour cells in head and neck cancer.Cell death discovery · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Heterogeneity of cancer-associated fibroblasts and tumor-promoting roles in head and neck squamous cell carcinoma.Frontiers in molecular biosciences · 2024Review
- The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment.Cancers · 2023Review
- Diagnostic, Prognostic, and Therapeutic Role for Angiogenesis Markers in Head and Neck Squamous Cell Carcinoma: A Narrative Review.International journal of molecular sciences · 2023Review
- Metastasis and cancer associated fibroblasts: taking it up a NOTCH.Frontiers in cell and developmental biology · 2023Review
- Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway.Acta biochimica et biophysica Sinica · 2022Article
- Comprehensive Integrated Single-Cell Whole Transcriptome Analysis Revealed the p-EMT Tumor Cells-CAFs Communication in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2022Article
- Review
- Notch signaling in oral pre-cancer and oral cancer.Medical oncology (Northwood, London, England) · 2021Review
- Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- The vascular landscape of human cancer.The Journal of clinical investigation · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs.
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