Moreover, inhibition of S1P signaling by different strategies has been confirmed by multiple studies to inhibit the activity of HIF-1α and HIF-2α in ccRCC and other cancer cells [22,23,24,25] and both genetic and pharmacological inhibition of S1P signaling pathways induce anti-tumor activities in several ccRCC xenograft models [20,22,25,26,27,28]. Here, EPAS1 is linked to cancer.