ArticleCell communication and signaling : CCS2025
IgSF11-RAP1 signaling promotes cell migration and invasion of cutaneous melanoma.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- MTR4 deficiency attenuates abdominal aortic aneurysm progression through suppressing VSMC senescence via the MTR4-RAP1a axis.iScience · 2026Article
- The miR-146a/Human mutation · 2026Article
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9 authors.
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Abstract
backgroundAberrant cell adhesion signaling is known to either accelerate or inhibit cancer progression, but the underlying molecular basis has yet to be established. The immunoglobulin superfamily 11 (IgSF11) functions as a cell adhesion protein and is overexpressed in several types of cancer, including high-grade glioma. However, it remains unknown whether and how IgSF11 stimulates malignant phenotypes.
methodsUsing The Cancer Genome Atlas (TCGA), we first examined the expression of IgSF11 gene in various types of cancer tissues. Next, we developed an anti-hIgSF11 monoclonal antibody (mAb) and evaluated the clinicopathological significance of high IgSF11 expression in 187 cutaneous melanoma patients via immunohistochemistry using this selective mAb. We also generated human melanoma cell lines A375 and 888mel expressing IgSF11, as well as 888mel:IgSF11
resultsIgSF11 mRNA was highly expressed in glioblastoma tissues and skin cutaneous melanoma tissues, but not in other malignant tumors. High IgSF11 expression was observed in 57 out of the 187 melanoma cases (30.5%) and was significantly correlated with Clark's level and high budding, both of which are parameters of melanoma invasion. Using a series of established cell lines, we demonstrated that IgSF11 promotes melanoma cell migration and invasion, as well as the enrichment of a gene set associated with epithelial-mesenchymal transition (EMT). Importantly, we identified that IgSF11 forms a complex with RAS-associated protein 1 (RAP1). Furthermore, the L372-R378 region of IgSF11 was required for recruiting RAP1 and driving melanoma cell migration.
conclusionsWe found that IgSF11-RAP1 signaling facilitates the migration and invasion of melanoma cells. The identification of IgSF11-RAP1 machinery highlights a novel link between cell adhesion and signaling molecules in promoting the malignant phenotypes of melanoma and may serve as a promising therapeutic target for this malignancy.
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