TCF4 and nonpapillary renal cell carcinoma: In ccRCC, Zhao et al verified that SPOP functions as an activator of β-catenin/T-cell factor 4 (TCF4) signaling and promoted cell invasion and EMT.[17] Similarly, Li et al discovered that accumulating SPOP expression induced by hypoxia promotes tumorigenesis by regulating the degradation of Daxx, phosphatase and tensin homolog deleted on chromosome 10, and dual specificity phosphatase 7.[33] Based on these findings, the exact mechanisms for the anti- or pro-tumor effects of SPOP in different tumors deserve further confirmation.