Roles of calcium signaling in cancer metastasis to bone.

Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hypercalcemia, pathologic fractures, spinal cord compression, and even death. However, the underlying mechanisms of bone metastasis were not clear. The role of calcium (Ca 2+ ) in cancer cell proliferation, migration, and invasion has been well established. Interestingly, emerging evidence indicates that Ca 2+ signaling played a key role in bone metastasis, for it not only promotes cancer progression but also mediates osteoclasts and osteoblasts differentiation. Therefore, Ca 2+ signaling has emerged as a novel therapeutical target for cancer bone metastasis treatments. Here, the role of Ca 2+ channels and Ca 2+ -binding proteins including calmodulin and Ca 2+ -sensing receptor in bone metastasis, and the perspective of anti-cancer bone metastasis therapeutics via targeting the Ca 2+ signaling pathway are summarized.