ArticleOncogene2014
The MAPK pathway functions as a redundant survival signal that reinforces the PI3K cascade in c-Kit mutant melanoma.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- Molecular Mechanisms of KIT Receptor Dimerization and Oncogenic Activation Revealed by Multiscale Simulations.Journal of chemical information and modeling · 2026Article
- Activation of KIT signaling promotes early tumorigenesis through the AP-1 pathway in APC/TP53 double-knockout human colon organoids.Cell death & disease · 2026Article
- Review
- Competitive signaling and cellular communications in myocardial infarction response.Molecular biology reports · 2025Review
- Novel Germline KIT Variants in Families With Severe Piebaldism: Case Series and Literature Review.Journal of clinical laboratory analysis · 2024Review
- The Influence of Blue Light Exposure on Reconstructed 3-Dimensional Skin Model: Molecular Changes and Gene Expression Profile.JID innovations : skin science from molecules to population health · 2024Article
- Reversing Gray Hair: Inspiring the Development of New Therapies Through Research on Hair Pigmentation and Repigmentation Progress.International journal of biological sciences · 2023Review
- c-Kit Induces Migration of Triple-Negative Breast Cancer Cells and Is a Promising Target for Tyrosine Kinase Inhibitor Treatment.International journal of molecular sciences · 2022Article
- RAS pathway regulation in melanoma.Disease models & mechanisms · 2022Review
- Exosome application in tumorigenesis: diagnosis and treatment of melanoma.Medical oncology (Northwood, London, England) · 2022Review
- The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness.Frontiers in oncology · 2022Review
- Sorafenib treatment of metastatic melanoma with c-Kit aberration reduces tumor growth and promotes survival.Oncology letters · 2021Article
- Review
- Review
- UTRN inhibits melanoma growth by suppressing p38 and JNK/c-Jun signaling pathways.Cancer cell international · 2021Article
- Functional and Clinical Characterization of Tumor-Infiltrating T Cell Subpopulations in Hepatocellular Carcinoma.Frontiers in genetics · 2020Article
- Repurposing Ponatinib as a Potent Agent againstTheranostics · 2019Article
- Targeting the HGF/MET Axis Counters Primary Resistance to KIT Inhibition inJCO precision oncology · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulation of the c-Kit receptor tyrosine kinase has a critical role in the development and migration of melanocytes, and oncogenic c-Kit mutants contribute to the progression of some melanomas. c-Kit signalling activates the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways and their relative contribution to the activities of oncogenic and ligand-dependent c-Kit remains uncertain. We show that PI3K is a major regulator of MAPK activation in response to c-Kit activity and the dominant effector of c-Kit-driven melanocyte proliferation and melanoma survival. Nevertheless, inhibition of the PI3K pathway in c-Kit mutant melanoma cells did not replicate the apoptotic efficacy of the c-Kit inhibitor, imatinib mesylate. Instead, the simultaneous suppression of the PI3K and MAPK pathways promoted a strong synergistic apoptotic effect. These data indicate that MAPK functions as a redundant survival signal that reinforces the PI3K cascade in c-Kit mutant melanoma. Thus, the concurrent inhibition of PI3K and MAPK signalling is required to suppress oncogenic c-Kit activity and may provide an effective therapeutic strategy in c-Kit mutant melanomas.
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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.