RSPO1 and colorectal cancer: Several lines of evidence have reported that LGR4–6 enhances activity of Wnt/β-catenin signaling via binding to R-spondins.22, 23, 24 However, LGR5 was found to play a negative role in Wnt signaling in colorectal cancer,32, 33 suggesting that the exact roles of LGR4–6 in Wnt signaling and tumorigenesis appear to vary depending on the given cellular context.