RSPO2 and colorectal cancer: Intriguingly, two previous studies demonstrated that RSPO2 inhibits colorectal cancer growth through unique LGR5-mediated Wnt/β-catenin signaling negative feedback mechanism, and RSPO2-mediated suppression of noncanonical Wnt signaling also exerted an inhibitory effect on colon tumor metastasis (Wu et al., 2014; Dong et al., 2017).