Role of the Wnt signaling pathway in prostate cancer bone metastasis. Prostate cancer cells have both osteolytic and osteoblastic potential. Early in skeletal metastasis, prostate cancer cells produce pro-osteolytic factors such as receptor activator of NFkB ligand (RANKL), interleukin-6 (IL-6) and parathyroid hormone-related protein (PTHrP) that stimulate osteoclastogenesis and also produce an inhibitor of osteoblastic activity, dickkopf-1 (DKK1). The resulting osteolytic activity releases growth factors from the bone and alters the bone microenvironment, which in turn alters the phenotype of prostate cancer cells. The prostate cancer cells start to produce osteoblastic factors such as bone morphogenetic proteins (BMP), PTHrP (which can act as an anabolic factor) and factors that inhibit osteclastogenic activity, such as, osteoprotegerin (OPG), which blocks RANKL. Additionally, DKK-1 expression is decreased resulting in the osteoblastic phase.