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The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche
Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that bot...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099066/ https://www.ncbi.nlm.nih.gov/pubmed/32218432 http://dx.doi.org/10.1038/s41467-020-15357-y |
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author | Ataca, Dalya Aouad, Patrick Constantin, Céline Laszlo, Csaba Beleut, Manfred Shamseddin, Marie Rajaram, Renuga Devi Jeitziner, Rachel Mead, Timothy J. Caikovski, Marian Bucher, Philipp Ambrosini, Giovanna Apte, Suneel S. Brisken, Cathrin |
author_facet | Ataca, Dalya Aouad, Patrick Constantin, Céline Laszlo, Csaba Beleut, Manfred Shamseddin, Marie Rajaram, Renuga Devi Jeitziner, Rachel Mead, Timothy J. Caikovski, Marian Bucher, Philipp Ambrosini, Giovanna Apte, Suneel S. Brisken, Cathrin |
author_sort | Ataca, Dalya |
collection | PubMed |
description | Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation. |
format | Online Article Text |
id | pubmed-7099066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70990662020-03-30 The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche Ataca, Dalya Aouad, Patrick Constantin, Céline Laszlo, Csaba Beleut, Manfred Shamseddin, Marie Rajaram, Renuga Devi Jeitziner, Rachel Mead, Timothy J. Caikovski, Marian Bucher, Philipp Ambrosini, Giovanna Apte, Suneel S. Brisken, Cathrin Nat Commun Article Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation. Nature Publishing Group UK 2020-03-26 /pmc/articles/PMC7099066/ /pubmed/32218432 http://dx.doi.org/10.1038/s41467-020-15357-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ataca, Dalya Aouad, Patrick Constantin, Céline Laszlo, Csaba Beleut, Manfred Shamseddin, Marie Rajaram, Renuga Devi Jeitziner, Rachel Mead, Timothy J. Caikovski, Marian Bucher, Philipp Ambrosini, Giovanna Apte, Suneel S. Brisken, Cathrin The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche |
title | The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche |
title_full | The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche |
title_fullStr | The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche |
title_full_unstemmed | The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche |
title_short | The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche |
title_sort | secreted protease adamts18 links hormone action to activation of the mammary stem cell niche |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099066/ https://www.ncbi.nlm.nih.gov/pubmed/32218432 http://dx.doi.org/10.1038/s41467-020-15357-y |
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