Functional analysis of Arl4c reveals its role in canine melanoma proliferation and migration

Abstract ADP ribosylation factor like 4c (Arl4c), a member of the small GTPase superfamily, has been implicated in tumor progression in various human cancers. However, its role in canine cancers remains largely unexplored. In this study, we demonstrated that Arl4c exhibits significant oncogenic activity in canine melanoma. Immunohistochemical analysis of canine clinical tumor samples indicated that Arl4c is highly expressed in canine melanoma. Functional assays in canine melanoma cell lines showed that Arl4c overexpression promotes cell proliferation and migration. Furthermore, a bioinformatics analysis identified a novel association between Arl4c and the nuclear factor kappa B (NF-κB) signaling pathway, subsequent experimental validation using Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) confirmed that Arl4c positively regulates NF-κB pathway activation, linking it to key tumorigenic mechanisms. These findings establish Arl4c as a pro-tumorigenic factor in canine melanoma and underscore its potential as both a diagnostic biomarker and a therapeutic target in veterinary oncology. Our study not only highlights Arl4c's role in canine tumorigenesis, but also reinforces the value canine models for informing novel treatment strategies for human cancers.