ArticleCancer science2016
Notch4+ cancer stem-like cells promote the metastatic and invasive ability of melanoma.
Article in Cancer science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- The expanding landscape of Deltex: signaling crosstalk and clinical implications.Cellular and molecular life sciences : CMLS · 2026Review
- NOTCH4 as a driver of epithelial-mesenchymal transition, angiogenesis, and stromal remodeling in lung adenocarcinoma: integrated transcriptomic and protein-level validation.Translational lung cancer research · 2026Article
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Review
- Construction and validation of a ubiquitination-related prognostic risk score signature in breast cancer.Heliyon · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- The lncRNA CADM2-AS1 promotes gastric cancer metastasis by binding with miR-5047 and activating NOTCH4 translation.Frontiers in pharmacology · 2024Article
- Deltex E3 ubiquitin ligase 4 promotes thyroid cancer progression through stearoyl-CoA desaturase 1.Functional & integrative genomics · 2023Article
- The DTX Protein Family:Cells · 2023Review
- The Clinical Application of Immunohistochemical Expression of Notch4 Protein in Patients with Colon Adenocarcinoma.International journal of molecular sciences · 2023Article
- Inactivation ofCancer research communications · 2022Article
- Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems.Stem cell reviews and reports · 2022Review
- Sec23a inhibits the self-renewal of melanoma cancer stem cells via inactivation of ER-phagy.Cell communication and signaling : CCS · 2022Article
- NOTCH4 mutation as predictive biomarker for immunotherapy benefits in NRAS wildtype melanoma.Frontiers in immunology · 2022Article
- Review
- Hypoxia increases the expression of stem cell markers in human osteosarcoma cells.Oncology letters · 2021Article
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives.Cancer management and research · 2021Review
- MAPK and Notch-Mediated Effects of Meso-Xanthin F199 Compounds on Proliferative Activity and Apoptosis of Human Melanocytes in Three-Dimensional Culture.BioMed research international · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphere formation in conditioned serum-free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor (tumorospheres) is considered useful for the enrichment of cancer stem-like cells, also known as tumor-initiating cells. We used a gene expression microarray to investigate the gene expression profile of melanoma cancer stem-like cells (MCSLCs). The results showed that MCSLCs highly expressed the following Notch signaling pathway molecules: Notch3 (NM_008716), Notch4 (NM_010929), Dtx4 (NM_172442), and JAG2 (NM_010588). Immunofluorescence staining showed tumorosphere cells highly expressed Notch4. Notch4(high) B16F10 cells were isolated by FACS, and Western blotting showed that high Notch4 expression is related to the expression of epithelial-mesenchymal transition (EMT)-associated proteins. Reduced invasive and migratory properties concomitant with the downregulation of the EMT markers Twist1, vimentin, and VE-cadherin and the overexpression of E-cadherin was observed in human melanoma A375 and MUM-2B cells. In these cells, Notch4 was also downregulated, both by Notch4 gene knockdown and by application of the γ-secretase inhibitor, DAPT. Mechanistically, the re-overexpression of Twist1 by the transfection of cells with a Twist1 expression plasmid led to an increase in VE-cadherin expression and a decrease in E-cadherin expression. Immunohistochemical analysis of 120 human melanoma tissues revealed a significant correlation between the high expression of Notch4 and the metastasis of melanoma. Taken together, our findings indicate that Notch4+ MCSLCs trigger EMT and promote the metastasis of melanoma cells.
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Registered trials
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