Show simple item record

dc.contributor.authorAtaca, Den_US
dc.contributor.authorAouad, Pen_US
dc.contributor.authorConstantin, Cen_US
dc.contributor.authorLaszlo, Cen_US
dc.contributor.authorBeleut, Men_US
dc.contributor.authorShamseddin, Men_US
dc.contributor.authorRajaram, RDen_US
dc.contributor.authorJeitziner, Ren_US
dc.contributor.authorMead, TJen_US
dc.contributor.authorCaikovski, Men_US
dc.contributor.authorBucher, Pen_US
dc.contributor.authorAmbrosini, Gen_US
dc.contributor.authorApte, SSen_US
dc.contributor.authorBrisken, Cen_US
dc.date.accessioned2020-05-22T12:29:14Z
dc.date.issued2020-03-26en_US
dc.identifier.citationNature communications, 2020, 11 (1), pp. 1571 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3624
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-020-15357-yen_US
dc.description.abstractEstrogens 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.en_US
dc.formatElectronicen_US
dc.format.extent1571 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.en_US
dc.typeJournal Article
dcterms.dateAccepted2020-02-28en_US
rioxxterms.versionofrecord10.1038/s41467-020-15357-yen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2020-03-26en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine control mechanisms
pubs.publication-statusPublisheden_US
pubs.volume11en_US
pubs.embargo.termsNot knownen_US
icr.researchteamEndocrine control mechanismsen_US
dc.contributor.icrauthorBrisken, Cathrinen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/