The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.
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Date
2020-03-26ICR Author
Author
Ataca, D
Aouad, P
Constantin, C
Laszlo, C
Beleut, M
Shamseddin, M
Rajaram, RD
Jeitziner, R
Mead, TJ
Caikovski, M
Bucher, P
Ambrosini, G
Apte, SS
Brisken, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Epithelium
Mammary Glands, Animal
Cell Line
Extracellular Matrix
Stem Cells
Animals
Mice, Inbred C57BL
Humans
Hormones
Glycoproteins
Fibronectins
Receptors, Progesterone
RNA, Messenger
Antigens, CD
Regeneration
Signal Transduction
Transcription, Genetic
Models, Biological
Female
Stem Cell Niche
Cell Self Renewal
ADAMTS Proteins
Research team
Endocrine control mechanisms
Language
eng
Date accepted
2020-02-28
License start date
2020-03-26
Citation
Nature communications, 2020, 11 (1), pp. 1571 - ?
Publisher
NATURE PUBLISHING GROUP