ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Notch signaling promotes growth and invasion in uveal melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Pooled it
- Immunohistochemical and molecular profiling of uveal melanoma: clinicopathological correlations from an Italian cohort.Pathologica · 2025Article
- NOTCH1 dimeric signaling is essential for T-cell leukemogenesis and leukemia maintenance.Blood · 2025Article
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Exploring recent advances in signaling pathways and hallmarks of uveal melanoma: a comprehensive review.Exploration of targeted anti-tumor therapy · 2025Review
- Identifying colorectal cancer subtypes and establishing a prognostic model using metabolic plasticity and ferroptosis genes.Scientific reports · 2024Article
- In Silico Pan-Cancer Analysis Reveals Prognostic Role of the Erythroferrone (ERFE) Gene in Human Malignancies.International journal of molecular sciences · 2023Article
- Article
- Recent advances in understanding the role of HES6 in cancers.Theranostics · 2022Review
- Biological implications and clinical potential of invasion and migration related miRNAs in glioma.Frontiers in integrative neuroscience · 2022Review
- Signal pathways of melanoma and targeted therapy.Signal transduction and targeted therapy · 2021Review
- Pluripotent Stem Cells: Cancer Study, Therapy, and Vaccination.Stem cell reviews and reports · 2021Review
- Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease.Cell death and differentiation · 2021Article
- Melanoma Plasticity: Promoter of Metastasis and Resistance to Therapy.Frontiers in oncology · 2021Review
- The Role of Non-Coding RNAs in Uveal Melanoma.Cancers · 2020Review
- Confocal Raman Spectral Imaging Study of DAPT, a γ-secretase Inhibitor, Induced Physiological and Biochemical Reponses in Osteosarcoma Cells.International journal of medical sciences · 2020Article
- Review
- Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy.Bioscience reports · 2018Review
- FOXP3 expression is modulated by TGF‑β1/NOTCH1 pathway in human melanoma.International journal of molecular medicine · 2018Article
- LGR5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial-mesenchymal transition through the Notch1 signaling pathway.Cancer medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine whether uveal melanoma, the most common primary intraocular malignancy in adults, requires Notch activity for growth and metastasis. EXPERIMENTAL
designExpression of Notch pathway members was characterized in primary tumor samples and in cell lines, along with the effects of Notch inhibition or activation on tumor growth and invasion.
resultsNotch receptors, ligands, and targets were expressed in all five cell lines examined and in 30 primary uveal melanoma samples. Interestingly, the three lines with high levels of baseline pathway activity (OCM1, OCM3, and OCM8) had their growth reduced by pharmacologic Notch blockade using the γ-secretase inhibitor (GSI) MRK003. In contrast, two uveal melanoma lines (Mel285 and Mel290) with very low expression of Notch targets were insensitive to the GSI. Constitutively active forms of Notch1 and Notch2 promoted growth of uveal melanoma cultures and were able to rescue the inhibitory effects of GSI. MRK003 treatment also inhibited anchorage-independent clonogenic growth and cell invasion and reduced phosphorylation levels of STAT3 and extracellular signal-regulated kinase (Erk)1/2. Suppression of canonical Notch activity using short hairpin RNA targeting Notch2 or CBF1 was also able to reduce tumor growth and invasion. Finally, intraocular xenograft growth was significantly decreased by GSI treatment.
conclusionOur findings suggest that Notch plays an important role in inducing proliferation and invasion in uveal melanoma and that inhibiting this pathway may be effective in preventing tumor growth and metastasis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.