ArticleThe Journal of biological chemistry2008
The ectodomain shedding of E-cadherin by ADAM15 supports ErbB receptor activation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 188 citations in OpenAlex.
- Phase II trial of dacomitinib in patients with HER2-positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2016Trial
- Dynamic modulation of intercellular adhesion mediated by matriptase-EPCAM/Trop-2 axes is critical for cell extrusion, division, and collective migration.Cell adhesion & migration · 2026Article
- Soluble E-cadherin-CXCL1-CXCR2 axis as a therapeutic vulnerability in inflammatory breast cancer brain metastasis.Neuro-oncology · 2026Article
- Article
- A Disintegrin and Metalloprotease 15 (ADAM15) as a Potential Predictor of Distant Metastasis in Colorectal Cancer (CRC).Journal of clinical medicine · 2025Article
- Apoptotic Caspases-3 and -7 Cleave Extracellular Domains of Membrane-Bound Proteins from MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2025Article
- TMEM52B-derived peptides inhibit generation of soluble E-cadherin and EGFR activity to suppress colon cancer growth and early metastasis.Journal of translational medicine · 2025Article
- Role of E-cadherin in epithelial barrier dysfunction: implications for bacterial infection, inflammation, and disease pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin.Scientific reports · 2024Article
- Role of ADAM and ADAMTS proteases in pathological tissue remodeling.Cell death discovery · 2023Review
- Identification and Characterization of an HtrA Sheddase Produced byInternational journal of molecular sciences · 2023Article
- Identification of membrane proteins regulated by ADAM15 by SUSPECS proteomics.Frontiers in molecular biosciences · 2023Article
- Dual role of E-cadherin in cancer cells.Tissue barriers · 2022Review
- Plasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis.International journal of molecular sciences · 2022Review
- Integrin α3/α6 and αV are implicated in ADAM15-activated FAK and EGFR signalling pathway individually and promote non-small-cell lung cancer progression.Cell death & disease · 2022Article
- Article
- Proteolytic Landscapes in Gastric Pathology and Cancerogenesis.International journal of molecular sciences · 2022Review
- Mechanical disruption of E-cadherin complexes with epidermal growth factor receptor actuates growth factor-dependent signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Control ofFrontiers in cellular and infection microbiology · 2022Article
- Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The zinc-dependent disintegrin metalloproteinases (a disintegrin and metalloproteinases (ADAMs) have been implicated in several disease processes, including human cancer. Previously, we demonstrated that the expression of a catalytically active member of the ADAM family, ADAM15, is associated with the progression of prostate and breast cancer. The accumulation of the soluble ectodomain of E-cadherin in human serum has also been associated with the progression of prostate and breast cancer and is thought to be mediated by metalloproteinase shedding. Utilizing two complementary models, overexpression and stable short hairpin RNA-mediated knockdown of ADAM15 in breast cancer cells, we demonstrated that ADAM15 cleaves E-cadherin in response to growth factor deprivation. We also demonstrated that the extracellular shedding of E-cadherin was abrogated by a metalloproteinase inhibitor and through the introduction of a catalytically inactive mutation in ADAM15. We have made the novel observation that this soluble E-cadherin fragment was found in complex with the HER2 and HER3 receptors in breast cancer cells. These interactions appeared to stabilize HER2 heterodimerization with HER3 and induced receptor activation and signaling through the Erk pathway, supporting both cell migration and proliferation. In this study, we provide evidence that ADAM15 catalyzes the cleavage of E-cadherin to generate a soluble fragment that in turn binds to and stimulates ErbB receptor signaling.
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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.