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| Item Type: | Article |
|---|---|
| Title: | Combined Wnt/β-catenin, met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome |
| Creators Name: | Holland, J.D., Györffy, B., Vogel, R., Eckert, K., Valenti, G., Fang, L., Lohneis, P., Elezkurtaj, S., Ziebold, U. and Birchmeier, W. |
| Abstract: | 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. |
| Keywords: | Biological Tumor Markers, Breast Neoplasms, CXCR4 Receptors, Chemokine CXCL12, Experimental Mammary Neoplasms, Genetic Therapy, Hepatocyte Growth Factor, Prognosis, Proto-Oncogene Proteins c-met, Wnt Signaling Pathway, beta Catenin, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 5 |
| Number: | 5 |
| Page Range: | 1214-1227 |
| Date: | 12 December 2013 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2013.11.001 |
| PubMed: | View item in PubMed |
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