VHL and nonpapillary renal cell carcinoma: Cyclin D1 is an important regulator of cell-cycle progression, and in vitro and in vivo data have demonstrated that HIF-2α-only-expressing ccRCC cells proliferate faster than their HIF-2α and HIF-1α co-expressing counterparts.42, 43 Therefore, we next assessed cell proliferation in SphK1-silenced VHL-defective ccRCC cells.