ArticleJCI insight2022
ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Methyltransferase-like 7B promotes M2-like macrophage polarization in lung adenocarcinoma via upregulating human epidermal growth factor receptor 3 expression and secretion.Oncology letters · 2026Article
- Targeting the EpCAM-AXL axis to overcome drug resistance in lung cancer.Molecular oncology · 2026Article
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- Dapagliflozin Inhibits Thrombin Induced ADAM17 Phosphorylation and Downstream ERK/p-c-Jun-mediated CTGF Induction to Prevent Neointimal Hyperplasia.Cardiovascular drugs and therapy · 2026Article
- Characterization of the D8P1C1 Anti-ADAM17 Inhibitory Monoclonal Antibody and Generation of Its Bispecific T-Cell Engager Derivative.International journal of molecular sciences · 2026Article
- M1 Macrophage-Derived Small Extracellular Vesicles as Synergistic Nanotherapeutics: Harnessing Intrinsic Anticancer Activity and Drug Delivery Capacity.Journal of extracellular vesicles · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Context-dependent regulation of IL-6 in exercise and colorectal cancer cachexia.Frontiers in oncology · 2026Review
- The CXCL9/SPP1 polarity axis in tumor-associated macrophages: immunoregulatory and prognostic significance in non-small cell lung cancer.Frontiers in immunology · 2026Article
- Article
- Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025Review
- Fibroblast EGFR signaling mediates ricin toxin-induced acute lung injury via EGR1/CXCL1 axis.Archives of toxicology · 2025Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- CD147 regulates the Rap1 signaling pathway to promote proliferation, migration, and invasion, and inhibit apoptosis in colorectal cancer cells.Scientific reports · 2025Article
- Targeted approach to determine the impact of cancer-associated protease variants.Science advances · 2025Article
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids.Scientific reports · 2024Article
- B7-H3 enhances colorectal cancer progression by regulating HB-EGF via HIF-1α.Journal of gastrointestinal oncology · 2024Article
- mInternational journal of oncology · 2024Article
- Correlation of MR-Based Metabolomics and Molecular Profiling in the Tumor Microenvironment of Temozolomide-Treated Orthotopic GL261 Glioblastoma in Mice.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages in the tumor microenvironment have a substantial impact on tumor progression. Depending on the signaling environment in the tumor, macrophages can either support or constrain tumor progression. It is therefore of therapeutic interest to identify the tumor-derived factors that control macrophage education. With this aim, we correlated the expression of A Disintegrin and Metalloproteinase (ADAM) proteases, which are key mediators of cell-cell signaling, to the expression of protumorigenic macrophage markers in human cancer cohorts. We identified ADAM17, a sheddase upregulated in many cancer types, as a protein of interest. Depletion of ADAM17 in cancer cell lines reduced the expression of several protumorigenic markers in neighboring macrophages in vitro as well as in mouse models. Moreover, ADAM17-/- educated macrophages demonstrated a reduced ability to induce cancer cell invasion. Using mass spectrometry-based proteomics and ELISA, we identified heparin-binding EGF (HB-EGF) and amphiregulin, shed by ADAM17 in the cancer cells, as the implicated molecular mediators of macrophage education. Additionally, RNA-Seq and ELISA experiments revealed that ADAM17-dependent HB-EGF ligand release induced the expression and secretion of CXCL chemokines in macrophages, which in turn stimulated cancer cell invasion. In conclusion, we provide evidence that ADAM17 mediates a paracrine EGFR-ligand-chemokine feedback loop, whereby cancer cells hijack macrophages to promote tumor progression.
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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.