JAG1 and cancer: In turn, osteoclasts have induced bone osteolysis and facilitated bone metastasis, accompanied by increased release of TGFβ; TGFβ-SMAD signaling has then further supported Jag1/IL-6-mediated interactions between the osteoblasts and the cancer cells, leading to a positive feedback loop that further promoted the metastatic process in bones [105] (Figure 1(B1)).