Treatment of melanoma cells with shRNA lentivirus to knockdown PDPN or with PDPN antagonist peptide CY12-RP2 could inhibit the Wnt/β-catenin pathway, which suggested that PDPN promoted melanoma cell proliferation, migration, and invasion at least partially via activation of the Wnt/β-catenin signaling pathway. Here, PDPN is linked to melanoma.