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Publication : Gpr177 deficiency impairs mammary development and prohibits Wnt-induced tumorigenesis.

First Author  Maruyama EO Year  2013
Journal  PLoS One Volume  8
Issue  2 Pages  e56644
PubMed ID  23457599 Mgi Jnum  J:199398
Mgi Id  MGI:5502502 Doi  10.1371/journal.pone.0056644
Citation  Maruyama EO, et al. (2013) Gpr177 deficiency impairs mammary development and prohibits Wnt-induced tumorigenesis. PLoS One 8(2):e56644
abstractText  Aberrant regulation of the Wnt pathway, essential for various developmental processes, is tightly linked to human breast cancers. By hijacking this evolutionary conserved signaling pathway, cancer cells acquire sustaining proliferation ability, leading to modification of physiologic properties necessary for tumor initiation and progression. An enormous wealth of knowledge on the importance of Wnt signaling in breast development and cancer has been obtained, but the cell types responsible for production of this proliferative signal operating within normal and malignant tissues remains poorly understood. Here we report that Wnt production mediated by Gpr177 is essential for mammary morphogenesis. The loss of Gpr177 interferes with mammary stem cells, leading to deficiencies in cell proliferation and differentiation. Genetic analysis further demonstrates an indispensable role of Gpr177 in Wnt-induced tumorigenesis. The Gpr177-deficiency mice are resistant to malignant transformation. This study not only demonstrates the necessity of Wnt in mammary organogenesis but also provides a proof-of-principle for targeting of Gpr177 as a potential new treatment for human diseases with aberrant Wnt stimulation.
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