Jagged1 promotes breast cancer bone metastasis

Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway’s contribution to metastasis remains unknown. The objective of this study [1] was to investigate the role of Notch signaling in the development of bone metastasis of breast cancer. The authors report that Notch ligand Jagged1 is overexpressed in metastasic tumor cells and activates the Notch signaling pathway in stromal bone cells. This activation leads to IL-6 release from osteoblasts that promotes tumor growth. In parallel, Jagged1 Notch activation in preosteoclasts stimulates differentiation and promotes osteolysis. Bone destruction is associated with the release of bone metastasis cytokine TGFβ that stimulates Jagged1 expression in bone tumor cells. Treatment with γ-secretase inhibitor reduced Jagged1-mediated bone metastasis by disrupting the Notch pathway in both stromal bone cells.

This study highlights a stroma-dependent mechanism for Notch signalling in breast cancer and provides evidence for γ-secretase inhibitor treatment of bone metastasis.

1. Sethi N et al. Cancer Cell 2011;19(2):192-205.