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.