Circulating tumor cells extravasate and seed into the bone (1). These cells interact with the osteogenic niche in the early stages of metastasis, through connexin 43 and E/N-cadherin, activating calcium and mTOR signaling to promote tumor growth (2). Later, during disease progression, tumor cells interact with the bone-resorbing osteoclasts through various mechanisms, thereby stimulating bone destruction (3). TGFβ and calcium are released as a consequence of osteoclastic bone destruction (4). This can enhance connexin 43 expression and provide more calcium to perpetuate the cycle of growth.