J 2016

SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling

KOLEDOVÁ, Zuzana, Xiaohong ZHANG, Charles STREULI, Robert B. CLARKE, Ophir D. KLEIN et. al.

Basic information

Original name

SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling

Authors

KOLEDOVÁ, Zuzana (203 Czech Republic, guarantor, belonging to the institution), Xiaohong ZHANG (826 United Kingdom of Great Britain and Northern Ireland), Charles STREULI (826 United Kingdom of Great Britain and Northern Ireland), Robert B. CLARKE (826 United Kingdom of Great Britain and Northern Ireland), Ophir D. KLEIN (840 United States of America), Zena WERB (840 United States of America) and Pengfei LU (156 China)

Edition

Proceedings of the National Academy of Sciences of the United States of America, Washington, National Academy of Sciences, 2016, 0027-8424

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 9.661

RIV identification code

RIV/00216224:14110/16:00088411

Organization unit

Faculty of Medicine

UT WoS

000383954700006

Keywords in English

branching morphogenesis; FGF signaling; EGF signaling; epithelial-stromal interactions; stromal microenvironment

Tags

Tags

International impact, Reviewed
Změněno: 5/12/2016 16:16, Ing. Mgr. Věra Pospíšilíková

Abstract

V originále

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 themutant 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.

Links

EE2.3.30.0037, research and development project
Name: Zaměstnáním nejlepších mladých vědců k rozvoji mezinárodní spolupráce
GJ16-20031Y, research and development project
Name: Signalizace FGF ve fibroblastech mléčné žlázy a její úloha ve vývoji a nádorech mléčné žlázy
Investor: Czech Science Foundation
ROZV/20/LF/2015, interní kód MU
Name: LF - Příspěvek IP 2015
Investor: Ministry of Education, Youth and Sports of the CR