β-catenin is translocated to the nucleus and stimulates expression of target genes that drive differentiation of the cells into osteoblasts.(36) Enhancement of Wnt signaling by lithium chloride treatment or by overexpression of Wnt3a in bone inhibited bone destruction and reduced tumor burden in a murine models of myeloma.(37,38) Myeloma cells interfere with Wnt-mediated bone formation by secreting DKK-1, a protein that binds to Wnt receptors and competes with Wnt binding to its receptor (Fig. 1). Here, DKK1 is linked to plasma cell myeloma.