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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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.
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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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