In particular, the hyperactivation of MAPKs pathways is associated with the over-expression of the transcription factor ERK that in turn leads to the over-expression of several genes involved in tumor development, including MMPs, TGFβ, and Osteopontin (OPN), whose role in melanoma is fundamental for the tumor invasion and metastatic processes [32,33,34]. Here, SPP1 is linked to melanoma.