Furthermore, it has been reported that the aberrant and constitutively activation of oncogenic signaling pathways, such as MAPK/ERK, phosphatidylinositol 3-kinase (PI3K)/AKT, mutated microphthalmia-associated transcription factor (MITF), endothelin dependent signaling, and ROS/NFkB pathways, are involved in the enhanced expression of HIF-1α in melanoma cells, independently by oxygen levels (22, 26–29). This evidence concerns the gene PIK3CA and melanoma.