SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling
Koledova, Zuzana1,2,3,4; Zhang, Xiaohong1,2; Streuli, Charles1,2; Clarke, Robert B.5; Klein, Ophir D.6,7,8,9; Werb, Zena10; Lu, Pengfei4
2016-09-27
发表期刊PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN0027-8424
卷号113期号:39页码:E5731-E5740
发表状态已发表
DOI10.1073/pnas.1611532113
摘要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.
关键词branching morphogenesis FGF signaling EGF signaling epithelial-stromal interactions stromal microenvironment
收录类别SCI
语种英语
资助项目Medical Research Council[MR/L011840/1]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000383954700006
出版者NATL ACAD SCIENCES
WOS关键词GROWTH-FACTOR RECEPTOR ; BRANCHING MORPHOGENESIS ; EXTRACELLULAR-MATRIX ; DISTINCT ROLES ; BREAST-CANCER ; IGF-I ; GLAND ; FGF ; GENE ; DIFFERENTIATION
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1701
专题生命科学与技术学院_PI研究组_吕鹏飞组
通讯作者Werb, Zena; Lu, Pengfei
作者单位1.Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
2.Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England
3.Masaryk Univ, Fac Med, Dept Histol & Embryol, Brno 62500, Czech Republic
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
5.Univ Manchester, Inst Canc Sci, Breast Canc Now Res Unit, Manchester Canc Res Ctr, Manchester M20 4QL, Lancs, England
6.Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA
7.Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
8.Univ Calif San Francisco, Program Craniofacial Biol, San Francisco, CA 94143 USA
9.Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA
10.Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
第一作者单位生命科学与技术学院
通讯作者单位生命科学与技术学院
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Koledova, Zuzana,Zhang, Xiaohong,Streuli, Charles,et al. SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2016,113(39):E5731-E5740.
APA Koledova, Zuzana.,Zhang, Xiaohong.,Streuli, Charles.,Clarke, Robert B..,Klein, Ophir D..,...&Lu, Pengfei.(2016).SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,113(39),E5731-E5740.
MLA Koledova, Zuzana,et al."SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113.39(2016):E5731-E5740.
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