Mutual regulation between melanoma cells and ECs under hypoxic conditions also involves functional regulators of HIF-1, which influence the angiogenic components of the cancer cell secretome including endothelin-1 and RLIP76 (Ral-interacting protein of 76 kDa) signaling, which in turn activate HIF-mediated VEGFA and VEGFC expression. The gene discussed is VEGFA; the disease is melanoma.