ArticleBMC cancer2014
Constitutive activation of the ERK pathway in melanoma and skin melanocytes in Grey horses.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 25 citations in OpenAlex.
- Probing Wnt pathway and functional signal in equine melanocytic neoplasms through quantitative proteomics and immunohistochemistry.BMC veterinary research · 2025Article
- Recent Issues in the Development and Application of Targeted Therapies with Respect to Individual Animal Variability.Animals : an open access journal from MDPI · 2025Review
- Article
- Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway.International journal of molecular sciences · 2024Article
- White horses - non-coding sequences drive premature hair greying and predisposition to melanoma.Upsala journal of medical sciences · 2024Review
- Interventions for treatment of cutaneous melanoma in horses: a structured literature review.Veterinary research communications · 2023Review
- Equine Melanocytic Tumors: A Narrative Review.Animals : an open access journal from MDPI · 2023Review
- Model Systems for the Study of Malignant Melanoma.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Cross-species analysis of enhancer logic using deep learning.Genome research · 2020Article
- Spontaneously occurring melanoma in animals and their relevance to human melanoma.The Journal of pathology · 2020Review
- Identification of prognostic gene biomarkers for metastatic skin cancer using data mining.Biomedical reports · 2020Article
- PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade.PloS one · 2020Article
- Cholinergic α5 nicotinic receptor is involved in the proliferation and invasion of human prostate cancer cells.Oncology reports · 2020Article
- High-resolution population structure and runs of homozygosity reveal the genetic architecture of complex traits in the Lipizzan horse.BMC genomics · 2019Article
- The MeLiM Minipig: An Original Spontaneous Model to Explore Cutaneous Melanoma Genetic Basis.Frontiers in genetics · 2017Review
- Cross-species models of human melanoma.The Journal of pathology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConstitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses.
methodsGrey horse melanoma tumours, cell lines and normal skin melanocytes were analyzed with help of indirect immunofluorescence and immunoblotting for the expression of phospho-ERK1/2 in comparison to that in non-grey horse and human counterparts. The mutational status of BRAF, RAS, GNAQ, GNA11 and KIT genes in Grey horse melanomas was determined by direct sequencing. The effect of RAS, RAF and PI3K/AKT pathways on the activation of the ERK signaling in Grey horse melanoma cells was investigated with help of specific inhibitors and immunoblotting. Individual roles of RAF and RAS kinases on the ERK activation were examined using si-RNA based approach and immunoblotting.
resultsWe found that the ERK pathway is constitutively activated in Grey horse melanoma tumours and cell lines in the absence of somatic activating mutations in BRAF, RAS, GNAQ, GNA11 and KIT genes or alterations in the expression of the main components of the pathway. The pathway is mitogenic and is mediated by BRAF, CRAF and KRAS kinases. Importantly, we found high activation of the ERK pathway also in epidermal melanocytes, suggesting a general predisposition to melanomagenesis in these horses.
conclusionsThese findings demonstrate that the presence of the intronic 4.6 kb duplication in STX17 is strongly associated with constitutive activation of the ERK pathway in melanocytic cells in Grey horses in the absence of somatic mutations commonly linked to the activation of this pathway during melanomagenesis. These findings are consistent with the universal importance of the ERK pathway in melanomagenesis and may have valuable implications for human melanoma research.
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