@article{88281,
  keywords = {Animals, signal transduction, Membrane Proteins, Ligands, Mice, Cell Differentiation, Transforming Growth Factor beta, Calcium-Binding Proteins, Osteoblasts, 3T3 Cells, Enzyme Inhibitors, Receptors, Notch, Intercellular Signaling Peptides and Proteins, Interleukin-6, Bone Neoplasms, Jagged-1 Protein, Serrate-Jagged Proteins, Mammary Neoplasms, Experimental, Smad Proteins, Amyloid Precursor Protein Secretases},
  author = {Nilay Sethi and Xudong Dai and Christopher Winter and Yibin Kang},
  title = {Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells.},
  abstract = {<p>Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway{\textquoteright}s contribution to metastasis remains unknown. Here, we report that the Notch ligand Jagged1 is a clinically and functionally important mediator of bone metastasis by activating the Notch pathway in bone cells. Jagged1 promotes tumor growth by stimulating IL-6 release from osteoblasts and directly activates osteoclast differentiation. Furthermore, Jagged1 is a potent downstream mediator of the bone metastasis cytokine TGFβ that is released during bone destruction. Importantly, γ-secretase inhibitor treatment reduces Jagged1-mediated bone metastasis by disrupting the Notch pathway in stromal bone cells. These findings elucidate a stroma-dependent mechanism for Notch signaling in breast cancer and provide rationale for using γ-secretase inhibitors for the treatment of bone metastasis.</p>
},
  year = {2011},
  journal = {Cancer Cell},
  volume = {19},
  pages = {192-205},
  month = {02/2011},
  issn = {1878-3686},
  doi = {10.1016/j.ccr.2010.12.022},
  language = {eng},
}