ArticleDevelopment (Cambridge, England)2013
Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin β1.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 104 citations in OpenAlex.
- Extracellular Matrix Viscoelasticity Regulates Mammary Branching Morphogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular Regulatory Mechanisms of Mammary Gland Development: A Review.Animals : an open access journal from MDPI · 2025Review
- Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.Developmental cell · 2025Article
- The role and regulation of integrins in cell migration and invasion.Nature reviews. Molecular cell biology · 2025Review
- MMP14 as a central mediator of TGF-β1-induced extracellular matrix remodeling in graves' orbitopathy.Frontiers in endocrinology · 2025Article
- Exploring the role of ITGB6: fibrosis, cancer, and other diseases.Apoptosis : an international journal on programmed cell death · 2024Review
- Review
- The Mammary Gland: Basic Structure and Molecular Signaling during Development.International journal of molecular sciences · 2022Review
- Identification of amino acid residues in the MT-loop of MT1-MMP critical for its ability to cleave low-density lipoprotein receptor.Frontiers in cardiovascular medicine · 2022Article
- Analysis of the expression and prognostic value of MT1-MMP, β1-integrin and YAP1 in glioma.Open medicine (Warsaw, Poland) · 2022Article
- Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.International journal of molecular sciences · 2021Review
- Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo.Cells · 2021Article
- Liver-Specific Overexpression of Prostasin Attenuates High-Fat Diet-Induced Metabolic Dysregulation in Mice.International journal of molecular sciences · 2021Article
- The androgen receptor/filamin A complex as a target in prostate cancer microenvironment.Cell death & disease · 2021Article
- Hold on or Cut? Integrin- and MMP-Mediated Cell-Matrix Interactions in the Tumor Microenvironment.International journal of molecular sciences · 2020Review
- The not-so-sweet side of sugar: Influence of the microenvironment on the processes that unleash cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Fgf10/Fgfr2b Signaling in Mammary Gland Development, Homeostasis, and Cancer.Frontiers in cell and developmental biology · 2020Review
- DNMT1 recruited by EZH2-mediated silencing of miR-484 contributes to the malignancy of cervical cancer cells through MMP14 and HNF1A.Clinical epigenetics · 2019Article
- Matrix metalloproteinase 1 modulates invasive behavior of tracheal branches during entry intoeLife · 2019Article
- MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues.Cells · 2019Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Epithelial cell invasion through the extracellular matrix (ECM) is a crucial step in branching morphogenesis. The mechanisms by which the mammary epithelium integrates cues from the ECM with intracellular signaling in order to coordinate invasion through the stroma to make the mammary tree are poorly understood. Because the cell membrane-bound matrix metalloproteinase Mmp14 is known to play a key role in cancer cell invasion, we hypothesized that it could also be centrally involved in integrating signals for mammary epithelial cells (MECs) to navigate the collagen 1 (CL-1)-rich stroma of the mammary gland. Expression studies in nulliparous mice that carry a NLS-lacZ transgene downstream of the Mmp14 promoter revealed that Mmp14 is expressed in MECs at the tips of the branches. Using both mammary organoids and 3D organotypic cultures, we show that MMP activity is necessary for invasion through dense CL-1 (3 mg/ml) gels, but dispensable for MEC branching in sparse CL-1 (1 mg/ml) gels. Surprisingly, however, Mmp14 without its catalytic activity was still necessary for branching. Silencing Mmp14 prevented cell invasion through CL-1 and disrupted branching altogether; it also reduced integrin β1 (Itgb1) levels and attenuated MAPK signaling, disrupting Itgb1-dependent invasion/branching within CL-1 gels. FRET imaging revealed that Mmp14 associates directly with Itgb1. We identified a domain of Mmp14 that is required for modulating the levels of Itgb1, MEC signaling and the rate of invasion within CL-1. These results shed light on hitherto undescribed non-proteolytic activities of Mmp14 that are necessary for the Itgb1-dependent biochemical and mechanical signals that regulate branching in the mammary epithelium.
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What OpenQuestion holds
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.