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Combined Wnt/β-catenin, met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome

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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. and Györffy, B. and Vogel, R. and Eckert, K. and Valenti, G. and Fang, L. and Lohneis, P. and Elezkurtaj, S. and 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 (U.S.A.)
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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