Importantly, knockdown of SUFU could restore the hampered proliferation and aggressiveness of A498 cells mediated by SPOP siRNA due to aberrant activation of SHH and WNT pathways, suggesting that SPOP–PTEN promotes tumorigenesis and progression in ccRCC partially by upregulating the activities of the SUFU-dependent SHH and WNT pathways (Fig. 8). The gene discussed is SHH; the disease is nonpapillary renal cell carcinoma.