ArticleThe Journal of biological chemistry2013
Chemical genetic screen reveals a role for desmosomal adhesion in mammary branching morphogenesis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Organoid Cultures for the Study of Mammary Biology and Breast Cancer: The Promise and Challenges.Cold Spring Harbor perspectives in medicine · 2024Review
- Article
- Adverse Effects of High Temperature On Mammary Alveolar Development In Vitro.Journal of mammary gland biology and neoplasia · 2022Article
- Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks.Journal of mammary gland biology and neoplasia · 2020Review
- A Cancer-Selective Zinc Ionophore Inspired by the Natural Product Naamidine A.ACS chemical biology · 2019Article
- Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Terminal End Bud: the Little Engine that Could.Journal of mammary gland biology and neoplasia · 2017Review
- Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.Genes & development · 2016Article
- Heterotypic control of basement membrane dynamics during branching morphogenesis.Developmental biology · 2015Review
- Adhesion in mammary development: novel roles for E-cadherin in individual and collective cell migration.Current topics in developmental biology · 2015Review
- Dioxin exposure blocks lactation through a direct effect on mammary epithelial cells mediated by the aryl hydrocarbon receptor repressor.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Article
- Bis-aryloxadiazoles as effective activators of the aryl hydrocarbon receptor.Bioorganic & medicinal chemistry letters · 2014Article
- Ductal barriers in mammary epithelium.Tissue barriers · 2013Review
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Authors and funding
10 authors.
Funding
Abstract
During the process of branching morphogenesis, the mammary gland undergoes distinct phases of remodeling to form an elaborate ductal network that ultimately produces and delivers milk to newborn animals. These developmental events rely on tight regulation of critical cellular pathways, many of which are probably disrupted during initiation and progression of breast cancer. Transgenic mouse and in vitro organoid models previously identified growth factor signaling as a key regulator of mammary branching, but the functional downstream targets of these pathways remain unclear. Here, we used purified primary mammary epithelial cells stimulated with fibroblast growth factor-2 (FGF2) to model mammary branching morphogenesis in vitro. We employed a forward chemical genetic approach to identify modulators of this process and describe a potent compound, 1023, that blocks FGF2-induced branching. In primary mammary epithelial cells, we used lentivirus-mediated knockdown of the aryl hydrocarbon receptor (AHR) to demonstrate that 1023 acts through AHR to block branching. Using 1023 as a tool, we identified desmosomal adhesion as a novel target of AHR signaling and show that desmosomes are critical for AHR agonists to block branching. Our findings support a functional role for desmosomes during mammary morphogenesis and also in blocking FGF-induced invasion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.