ArticleInternational journal of biological sciences2014
Targeting the sheddase activity of ADAM17 by an anti-ADAM17 antibody D1(A12) inhibits head and neck squamous cell carcinoma cell proliferation and motility via blockage of bradykinin induced HERs transactivation.
Article in International journal of biological sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- Article
- Integrated single-cell genomics, transcriptomics, and pathomics to identify potential biomarkers in muscle-invasive bladder cancer.Translational andrology and urology · 2025Article
- ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases.Frontiers in pharmacology · 2025Review
- Fully human monoclonal antibody targeting the cysteine-rich substrate-interacting region of ADAM17 on cancer cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Fully human monoclonal antibody targeting activated ADAM10 on colorectal cancer cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity.Cellular and molecular life sciences : CMLS · 2023Article
- APPlications of amyloid-β precursor protein metabolites in macrocephaly and autism spectrum disorder.Frontiers in molecular neuroscience · 2023Review
- Pan-cancer analysis of ADAMs: A promising biomarker for prognosis and response to chemotherapy and immunotherapy.Frontiers in genetics · 2023Article
- A novel combination treatment of antiADAM17 antibody and erlotinib to overcome acquired drug resistance in non-small cell lung cancer through the FOXO3a/FOXM1 axis.Cellular and molecular life sciences : CMLS · 2022Article
- The role of tetraspanins pan-cancer.iScience · 2022Article
- Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?Cancers · 2022Review
- Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.Pathogens (Basel, Switzerland) · 2022Review
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
- Combined Radiochemotherapy: Metalloproteinases Revisited.Frontiers in oncology · 2021Review
- ADAM17 Mediates Hypoxia-Induced Keratinocyte Migration via the p38/MAPK Pathway.BioMed research international · 2021Article
- Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design.Biology · 2020Review
- ADAM-Mediated Signalling Pathways in Gastrointestinal Cancer Formation.International journal of molecular sciences · 2020Review
- A Bispecific Inhibitor of the EGFR/ADAM17 Axis Decreases Cell Proliferation and Migration of EGFR-Dependent Cancer Cells.Cancers · 2020Article
- Systematic Profiling of Immune Risk Model to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A disintegrin and metalloproteinase 17 (ADAM17) regulates key cellular processes including proliferation and migration through the shedding of a diverse array of substrates such as epidermal growth factor receptor (EGFR) ligands. ADAM17 is implicated in the pathogenesis of many diseases including rheumatoid arthritis and cancers such as head and neck squamous cell carcinoma (HNSCC). As a central mediator of cellular events, overexpressed EGFR is a validated molecular target in HNSCC. However, EGFR inhibition constantly leads to tumour resistance. One possible mechanism of resistance is the activation of alternative EGFR family receptors and downstream pathways via the release of their ligands. Here, we report that treating human HNSCC cells in vitro with a human anti-ADAM17 inhibitory antibody, D1(A12), suppresses proliferation and motility in the absence or presence of the EGFR tyrosine kinase inhibitor (TKI) gefitinib. Treatment with D1(A12) decreases both the endogenous and the bradykinin (BK)-stimulated shedding of HER ligands, accompanied by a reduction in the phosphorylation of HER receptors and downstream signalling pathways including STAT3, AKT and ERK. Knockdown of ADAM17, but not ADAM10, also suppresses HNSCC cell proliferation and migration. Furthermore, we show that heregulin (HRG) and heparin-binding epidermal growth factor like growth factor (HB-EGF) predominantly participate in proliferation and migration, respectively. Taken together, these results demonstrate that D1(A12)-mediated inhibition of cell proliferation, motility, phosphorylation of HER receptors and downstream signalling is achieved via reduced shedding of ADAM17 ligands. These findings underscore the importance of ADAM17 and suggest that D1(A12) might be an effective targeted agent for treating EGFR TKI-resistant HNSCC.
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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.