We next analyzed the level of GLUT-1 and cyclin D1, two well-established specific target proteins of HIF-2α in VHL-defective ccRCC.40, 41 Under normoxia and hypoxia, SphK1 silencing significantly reduced levels of both glucose transporter GLUT-1 (Figure 3b) and cyclin D1 (Figure 3c) in both cell lines. Here, VHL is linked to nonpapillary renal cell carcinoma.