SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling.
Affiliation
Faculty of Life Sciences, University of Manchester, Manchester M13 9PTIssue Date
2016-09-27
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The role of the local microenvironment in influencing cell behavior is central to both normal development and cancer formation. Here, we show that sprouty 1 (SPRY1) modulates the microenvironment to enable proper mammary branching morphogenesis. This process occurs through negative regulation of epidermal growth factor receptor (EGFR) signaling in mammary stroma. Loss of SPRY1 resulted in up-regulation of EGFR-extracellular signal-regulated kinase (ERK) signaling in response to amphiregulin and transforming growth factor alpha stimulation. Consequently, stromal paracrine signaling and ECM remodeling is augmented, leading to increased epithelial branching in the mutant gland. By contrast, down-regulation of EGFR-ERK signaling due to gain of Sprouty function in the stroma led to stunted epithelial branching. Taken together, our results show that modulation of stromal paracrine signaling and ECM remodeling by SPRY1 regulates mammary epithelial morphogenesis during postnatal development.Citation
SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling. 2016, 113 (39):E5731-40 Proc. Natl. Acad. Sci. U.S.A.Journal
Proceedings of the National Academy of Sciences of the United States of AmericaDOI
10.1073/pnas.1611532113PubMed ID
27621461Type
ArticleLanguage
enISSN
0027-8424ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1611532113
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