| First Author | Holland JD | Year | 2013 |
| Journal | Cell Rep | Volume | 5 |
| Issue | 5 | Pages | 1214-27 |
| PubMed ID | 24290754 | Mgi Jnum | J:206839 |
| Mgi Id | MGI:5553031 | Doi | 10.1016/j.celrep.2013.11.001 |
| Citation | Holland JD, et al. (2013) Combined Wnt/beta-catenin, Met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome. Cell Rep 5(5):1214-27 |
| abstractText | Prognosis for patients with estrogen-receptor (ER)-negative basal breast cancer is poor, and chemotherapy is currently the best therapeutic option. We have generated a compound-mutant mouse model combining the activation of beta-catenin and HGF (Wnt-Met signaling), which produced rapidly growing basal mammary gland tumors. We identified the chemokine system CXCL12/CXCR4 as a crucial driver of Wnt-Met tumors, given that compound-mutant mice also deficient in the CXCR4 gene were tumor resistant. Wnt-Met activation rapidly expanded a population of cancer-propagating cells, in which the two signaling systems control different functions, self-renewal and differentiation. Molecular therapy targeting Wnt, Met, and CXCR4 in mice significantly delayed tumor development. The expression of a Wnt-Met 322 gene signature was found to be predictive of poor survival of human patients with ER-negative breast cancers. Thus, targeting CXCR4 and its upstream activators, Wnt and Met, might provide an efficient strategy for breast cancer treatment. |
