LGR4 and cancer: In the premetastatic niche in vivo model, overexpression of DKK1 in human SCP46 cancer cells restored the serum level of human DKK1 protein inhibited by LGR4 knockdown (Supplemental Figure 6, C and D) and reversed the effects of LGR4 silencing on OP number and osteoclast number and activity (Figure 5, A and B, and Supplemental Figure 6E).