ArticleProceedings of the National Academy of Sciences of the United States of America2006
Phosphorylation of TNF-alpha converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 138 citations in OpenAlex.
- Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Sheddase activity of tumor necrosis factor-alpha converting enzyme is increased and prognostically valuable in head and neck cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009Trial
- Article
- ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection.Life science alliance · 2023Article
- Analysis of the epidermal growth factor receptor/phosphoinositide-dependent protein kinase-1 axis in tumor of the external auditory canal in response to epidermal growth factor stimulation.Laryngoscope investigative otolaryngology · 2022Article
- ADAM and ADAMTS disintegrin and metalloproteinases as major factors and molecular targets in vascular malfunction and disease.Advances in pharmacology (San Diego, Calif.) · 2022Article
- NOTCH1 Signalling: A key pathway for the development of high-risk chronic lymphocytic leukaemia.Frontiers in oncology · 2022Review
- Review
- Review
- Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways.iScience · 2021Article
- P2YOral oncology · 2020Article
- A Disintegrin and Metalloproteinase (ADAM) and ADAM with thrombospondin motifs (ADAMTS) family in vascular biology and disease.Biochemical pharmacology · 2019Review
- Structural and Functional Analyses of the Shedding Protease ADAM17 in HoxB8-Immortalized Macrophages and Dendritic-like Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Targeting Src attenuates peritoneal fibrosis and inhibits the epithelial to mesenchymal transition.Oncotarget · 2017Article
- Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer.The Prostate · 2016Article
- REG4 promotes peritoneal metastasis of gastric cancer through GPR37.Oncotarget · 2016Article
- A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems.Frontiers in physiology · 2016Review
- Src inhibition blocks renal interstitial fibroblast activation and ameliorates renal fibrosis.Kidney international · 2016Article
- Mechanisms of Invasion in Head and Neck Cancer.Archives of pathology & laboratory medicine · 2015Review
- International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].Pharmacological reviews · 2015Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors induce EGF receptor (EGFR) signaling, leading to the proliferation and invasion of cancer cells. Elucidation of the mechanism of EGFR activation by G protein-coupled receptors may identify new signaling paradigms. A gastrin-releasing peptide (GRP)/GRP receptor-mediated autocrine pathway was previously described in squamous cell carcinoma of head and neck. In the present study, we demonstrate that TNF-alpha converting enzyme (TACE), a disintegrin and metalloproteinse-17, undergoes a Src-dependent phosphorylation that regulates release of the EGFR ligand amphiregulin upon GRP treatment. Further investigation reveals the phosphatidylinositol 3-kinase (PI3-K) as the intermediate of c-Src and TACE, contributing to their association and TACE phosphorylation. Phosphoinositide-dependent kinase 1 (PDK1), a downstream target of PI3-K, has been identified as the previously undescribed kinase to directly phosphorylate TACE upon GRP treatment. These findings suggest a signaling cascade of GRP-Src-PI3-K-PDK1-TACE-amphiregulin-EGFR with multiple points of interaction, translocation, and phosphorylation. Furthermore, knockdown of PDK1 augmented the antitumor effects of the EGFR inhibitor erlotinib, indicating PDK1 as a therapeutic target to improve the clinical response to EGFR inhibitors.
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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.