The MAPK (RAF-MEK-ERK) signaling pathway is frequently activated in melanoma (35), and it can phosphorylate the downstream p90 ribosomal S6 kinase (RSK) (36), which activates fructose-2,6-bisphosphatase 2 (PFKFB2), an isoform of phosphofructokinase, increasing fructose-2,6-bisphosphate synthesis (a glycolytic intermediate) (37). This evidence concerns the gene PFKFB2 and melanoma.