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Integrative Phosphoproteomic Profiling Reveals Stage-Specific Signalling and Metabolism in Equine Melanocytic
Paitoon Srimontri1, Amornthep Kingkaw2, Nawarus Prapaiwan1
1Department of Clinical Science and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
Veterinary and Comparative Oncology
|April 17, 2026
Summary
This study reveals stage-specific molecular changes in equine melanocytic neoplasms (EMN), identifying key signaling pathways and metabolic alterations. Findings highlight potential biomarkers and therapeutic targets for aggressive equine melanoma.
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Biochemistry
Background:
- Equine melanocytic neoplasms (EMN) are aggressive tumors with high metastatic potential and few treatment options.
- The molecular drivers of EMN progression are not well understood, hindering therapeutic development.
Purpose of the Study:
- To perform an integrative phosphoproteomic analysis of EMN tissues to identify stage-specific alterations in signaling pathways and metabolism.
- To elucidate the molecular mechanisms underlying equine melanoma progression.
Main Methods:
- Phosphoproteomic analysis of 19 equine tissue samples (normal, early-stage EMN, severe-stage EMN) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Identification and differential expression analysis of 2035 phosphoproteins across disease stages.
Main Results:
- Early-stage EMN showed dysregulated inositol phosphate metabolism and PI3K-Akt pathway activation.
- Severe-stage EMN exhibited enhanced membrane trafficking, cytoskeletal remodeling, MAPK signaling, heightened proliferation, and altered Rap1 signaling.
- Metabolic reprogramming, including elevated glycolysis and NADPH production, and aberrant protein homeostasis were observed.
- Increased Dickkopf-3 (DKK3) expression in severe-stage EMN suggests a role in Wnt/β-catenin pathway activation and tumor progression.
Conclusions:
- Stage-specific molecular mechanisms in equine melanoma pathogenesis have been elucidated.
- Identified signaling pathways and proteins represent potential biomarkers and therapeutic targets for equine melanoma.
