Wnt signaling in bone metastasis: mechanisms and therapeutic opportunities

Bone metastasis frequently occurs in advanced cancer patients, who will develop osteogenic/osteolytic bone lesions in the late stage of the disease. Wnt signaling pathway, which is mainly grouped into the beta-catenin dependent pathway and beta-catenin independent pathway, is a well-organized cascade that has been reported to play important roles in a variety of physiological and pathological conditions, including bone metastasis. Regulation of Wnt signaling in bone metastasis involves multiple stages, including dissemination of primary tumor cells to bone, dormancy and outgrowth of metastatic tumor cells, and tumor-induced osteogenic and osteolytic bone destruction, suggesting the importance of Wnt signaling in bone metastasis pathology. In this review, we will introduce the involvement of Wnt signaling components in specific bone metastasis stages and summarize the promising Wnt modulators that have shown potential as bone metastasis therapeutics, in the hope to maximize the therapeutic opportunities of Wnt signaling for bone metastasis.