While investigating the presence of bidirectional autocrine/paracrine endothelin-1 (ET-1)/endothelin-1 receptor signalling in melanoma cells, blood and lymphatic endothelial cells, hypoxia was observed to enhance ET-1 expression regulating vascularization and cell motility through increased secretion of VEGF-A and VEGF-C in response to HIF-1α and HIF-2α [73]. Here, EPAS1 is linked to melanoma.