In our study, TRIM59-/ -macrophages mediated upregulation of the PI3K and ERK signaling pathways in B16 melanoma cells, promoting MMP-9 and Madcam1 expression and stimulating migration and invasion in vitro, as well as tumorigenesis, EMT, and metastasis in an in vivo tumor model. This evidence concerns the gene MADCAM1 and melanoma.