ArticleOncotarget2018
ADAM17 inhibition enhances platinum efficiency in ovarian cancer.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- The role of small extracellular vesicles in ovarian cancer drug resistance: from bench clues to clinical implications.Journal of ovarian research · 2026Review
- Function and Spatial Organization of Tumor-Invasive Human γδ T Cells-What Do We Know?European journal of immunology · 2025Review
- ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases.Frontiers in pharmacology · 2025Review
- Cisplatin resistance alters ovarian cancer spheroid formation and impacts peritoneal invasion.Frontiers in cell and developmental biology · 2025Article
- Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids.Scientific reports · 2024Article
- Fully human monoclonal antibody targeting the cysteine-rich substrate-interacting region of ADAM17 on cancer cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Article
- Molecular Determinants Involved in the Docking and Uptake of Tumor-Derived Extracellular Vesicles: Implications in Cancer.International journal of molecular sciences · 2024Review
- Inhibition of ADAM17 increases the cytotoxic effect of cisplatin in cervical spheroids and organoids.Frontiers in oncology · 2024Article
- Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab.Diagnostics (Basel, Switzerland) · 2022Article
- NGF/TRKA Promotes ADAM17-Dependent Cleavage of P75 in Ovarian Cells: Elucidating a Pro-Tumoral Mechanism.International journal of molecular sciences · 2022Article
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
- Article
- Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes.Bioscience reports · 2021Review
- ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids.Cancers · 2021Article
- Expression of ADAM Proteases in Bladder Cancer Patients with BCG Failure: A Pilot Study.Journal of clinical medicine · 2021Article
- Notch Signaling Pathway in Pancreatobiliary Tumors.Medicina (Kaunas, Lithuania) · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapeutic resistance evolves in about 70 % of ovarian cancer patients and is a major cause of death in this tumor entity. Novel approaches to overcome these therapeutic limitations are therefore highly warranted. A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in ovarian cancer and required for releasing epidermal growth factor receptor (EGFR) ligands like amphiregulin (AREG). This factor has recently been detected in ascites of advanced stage ovarian cancer patients. However, it is not well understood, whether and how ADAM17 might contribute to chemo resistance of ovarian cancer. In this study, we identified ADAM17 as an essential upstream regulator of AREG release under chemotherapeutic treatment in ovarian cancer cell lines and patient derived cells. In the majority of ovarian cancer cells cisplatin treatment resulted in enhanced ADAM17 activity, as shown by an increased shedding of AREG. Moreover, both mRNA and the protein content of AREG were dose-dependently increased by cisplatin exposure. Consequently, cisplatin strongly induced phosphorylation of ADAM17-downstream mediators, the EGFR and extracellular signal-regulated kinases (ERK). Phorbol 12-myristate 13-acetate (PMA), similarly to cisplatin, mediated AREG shedding and membrane fading of surface ADAM17. Inhibition of ADAM17 with either GW280264X or the anti-ADAM17 antibody D1 (A12) as well as silencing of ADAM17 by siRNA selectively reduced AREG release. Thus, ADAM17 inhibition sensitized cancer cells to cisplatin-induced apoptosis, and significantly reduced cell viability. Based on these findings, we propose that targeting of ADAM17 in parallel to chemotherapeutic treatment suppresses survival pathways and potentially diminish evolving secondary chemo resistance mechanisms.
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