ArticleProceedings of the National Academy of Sciences of the United States of America2013
ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 97 citations in OpenAlex.
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Contributions of T-helper 9 cells in endometriosis-associated inflammation and lesion growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Targeted shedding of extracellular membrane proteins by induced protease recruitment.bioRxiv : the preprint server for biology · 2026Article
- ADAM10 Knockout from Human Glioblastoma and Colon Cancer Cells Modulates Diverse Signalling Networks and Inhibits Tumour Growth In Vivo.International journal of molecular sciences · 2025Article
- Molecular mechanisms underlying the inhibition of cell migration and invasion in endometriosis: Advances in pharmacological research (Review).Biomedical reports · 2025Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- Inhibition of colorectal cancer progression through conformation-specific targeting of ADAM10 metalloprotease.Frontiers in oncology · 2025Article
- Human Retinal Progenitor Cell (hRPC) Migration in Three-Dimensional (3D) Environments of Varying Stiffness and Composition.Journal of tissue engineering and regenerative medicine · 2025Article
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters in collective cell migration of epithelial cells.Cell reports · 2024Article
- Bridging systems biology and tissue engineering: Unleashing the full potential of complex 3DBiophysics reviews · 2024Review
- A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.International journal of molecular sciences · 2023Article
- ADAM10 and ADAM17 regulate EGFR, c-Met and TNF RI signalling in liver regeneration and fibrosis.Scientific reports · 2021Article
- Proteolytic Cleavage of Receptor Tyrosine Kinases.Biomolecules · 2021Review
- Suppression of α-catenin and adherens junctions enhances epithelial cell proliferation and motility via TACE-mediated TGF-α autocrine/paracrine signaling.Molecular biology of the cell · 2021Article
- Computational Models for Diagnosing and Treating Endometriosis.Frontiers in reproductive health · 2021Review
- HER3-Receptor-Mediated STAT3 Activation Plays a Central Role in Adaptive Resistance toward Vemurafenib in Melanoma.Cancers · 2020Article
- Menstruation: science and society.American journal of obstetrics and gynecology · 2020Review
- ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling.The Journal of pathology · 2020Article
- Physiomimetic Models of Adenomyosis.Seminars in reproductive medicine · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
A Disintegrin and Metalloproteinases (ADAMs) are the principal enzymes for shedding receptor tyrosine kinase (RTK) ectodomains and ligands from the cell surface. Multiple layers of activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent ADAM "sheddase" function and our ability to predictably target that function in disease. This study uses combined measurement and computational modeling to examine how various growth factor environments influence sheddase activity and cell migration in the invasive disease of endometriosis. We find that ADAM-10 and -17 dynamically integrate numerous signaling pathways to direct cell motility. Data-driven modeling reveals that induced cell migration is a quantitative function of positive feedback through EGF ligand release and negative feedback through RTK shedding. Although sheddase inhibition prevents autocrine ligand shedding and resultant EGF receptor transactivation, it also leads to an accumulation of phosphorylated receptors (HER2, HER4, and MET) on the cell surface, which subsequently enhances Jnk/p38 signaling. Jnk/p38 inhibition reduces cell migration by blocking sheddase activity while additionally preventing the compensatory signaling from accumulated RTKs. In contrast, Mek inhibition reduces ADAM-10 and -17 activities but fails to inhibit compensatory signaling from accumulated RTKs, which actually enhances cell motility in some contexts. Thus, here we present a sheddase-based mechanism of rapidly acquired resistance to Mek inhibition through reduced RTK shedding that can be overcome with rationally directed combination inhibitor treatment. We investigate the clinical relevance of these findings using targeted proteomics of peritoneal fluid from endometriosis patients and find growth-factor-driven ADAM-10 activity and MET shedding are jointly dysregulated with disease.
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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.