We focused on the tumor suppressors RNF43 and ZNRF3, which are transmembrane E3 ubiquitin ligases expressed in LGR5+ stem cells that regulate WNT signals by targeting WNT receptors for degradation in an R-spondin-sensitive manner (Hao et al., 2012, Koo et al., 2012, Tsukiyama et al., 2015). This evidence concerns the gene RSPO1 and neoplasm.