Importantly, knockdown of SPOP reduces ccRCC cell ability of proliferation, migration, and invasion, which can be rescued through additional knockdown of SUFU as the result of elevated activities of SHH and WNT pathways, indicating that SPOP promotes tumorigenesis and progression via activating SUFU-dependent SHH and WNT signaling pathway. This evidence concerns the gene SUFU and nonpapillary renal cell carcinoma.