CCND1 and osteosarcoma: Besides, mRNA levels of Cyclin D1 and Cyclin E, two downstream target genes of β-catenin [13], were also reduced in cells with Lgr4 deficiency (Supplementary Figure  4(c)-4(d)), suggesting that Lgr4 is critical for the Wnt/β-catenin signaling activation in osteosarcoma cells.