ArticleGenes & development2013
The hemopexin domain of MMP3 is responsible for mammary epithelial invasion and morphogenesis through extracellular interaction with HSP90β.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 88 citations in OpenAlex.
- Machine learning identification of biomarkers for vascular endothelial damage in obstructive sleep apnea.Clinics (Sao Paulo, Brazil) · 2026Article
- Methyl gallate and hyaluronic acid-nanoconjugate targeting HSP90β for osteoarthritis therapy.Journal of nanobiotechnology · 2026Article
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- The Hsp90β Isoform: An Attractive Target for Drug Development.Medicinal research reviews · 2025Review
- Upregulation of MMP3 Promotes Cisplatin Resistance in Ovarian Cancer.International journal of molecular sciences · 2025Article
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Single-cell and spatial transcriptomics reveal pre-metastatic subsets and therapeutic targets in penile carcinoma.iScience · 2025Article
- YWHAB is regulated by IRX5 and inhibits the migration and invasion of breast cancer cells.Oncology letters · 2024Article
- Review
- Maggot Extract Inhibits Cell Migration and Tumor Growth by Targeting HSP90AB1 in Ovarian Cancer.Journal of clinical medicine · 2022Article
- Cytosolic Hsp90 Isoform-Specific Functions and Clinical Significance.Biomolecules · 2022Review
- Hsp90: From Cellular to Organismal Proteostasis.Cells · 2022Review
- Targeting extracellular Hsp90: A unique frontier against cancer.Frontiers in molecular biosciences · 2022Review
- The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance.Frontiers in cell and developmental biology · 2021Review
- Prostate cancer-derived MMP-3 controls intrinsic cell growth and extrinsic angiogenesis.Neoplasia (New York, N.Y.) · 2020Article
- Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice.Nutrients · 2020Article
- Recent aspects of the effects of zinc on human health.Archives of toxicology · 2020Review
- MicroRNA-18a-5p Suppresses Tumor GrowthFrontiers in oncology · 2020Article
- Pyridine-Containing Macrocycles Display MMP-2/9 Inhibitory Activity and Distinct Effects on Migration and Invasion of 2D and 3D Breast Cancer Models.International journal of molecular sciences · 2019Article
- Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Matrix metalloproteinases (MMPs) are crucial mediators in sculpting tissue architecture and are required for many physiological and pathological processes. MMP3 has been shown to regulate branching morphogenesis in the mammary gland. Ectopic expression of proteolytically active MMP3 in mouse mammary epithelia triggers supernumerary lateral branching and, eventually, tumors. Using a three-dimensional collagen-I (Col-1) gel assay that simulates epithelial invasion and branching, we show that it is the hemopexin domain that directs these processes. Using three different engineered constructs containing a variation on MMP3 structural domains, we confirmed the importance of the hemopexin domain also in primary organoids of the mammary gland. A proteomic screen of MMP3-binding partners surprisingly revealed that the intracellular chaperone heat-shock protein 90 β (HSP90β) is present extracellularly, and its interaction with the hemopexin domain of MMP3 is critical for invasion. Blocking of HSP90β with inhibitory antibodies added to the medium abolished invasion and branching. These findings shift the focus from the proteolytic activity of MMP3 as the central player to its hemopexin domain and add a new dimension to HSP90β's functions by revealing a hitherto undescribed mechanism of MMP3 regulation. Our data also may shed light on the failure of strategies to use MMP inhibitors in cancer treatment and other related disorders.
Indexed as
Identifiers
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.