ArticleJournal of cellular biochemistry2008
Generation of novel, secreted epidermal growth factor receptor (EGFR/ErbB1) isoforms via metalloprotease-dependent ectodomain shedding and exosome secretion.
Article in Journal of cellular biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 117 citations in OpenAlex.
- A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2017Trial
- Rhomboid protease RHBDL2 is a calcium-activated suppressor of EGFR signalling in keratinocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Review
- Soluble isoforms of EGFR family in breast cancer: Advances and clinical relevance (Review).Oncology letters · 2026Review
- Glioblastoma Cells Expressing Oncogenic EGFR Release Multiple Extracellular Vesicle Subpopulations Positive or Negative for EGFR.Journal of extracellular biology · 2026Article
- Extracellular vesicles decoying across host immunity.Journal of leukocyte biology · 2025Review
- Epidermal growth factor receptor contributes to indirect regulation of skeletal muscle mass by androgen.Endocrine journal · 2025Article
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- Suppression of Nasopharyngeal and Gastric Tumor Growth in a Mouse Model by Antibodies to Epstein-Barr Virus LMP1 Protein.Microorganisms · 2023Article
- Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression.Cancers · 2023Review
- How Driver Oncogenes Shape and Are Shaped by Alternative Splicing Mechanisms in Tumors.Cancers · 2023Review
- Review
- Recent Advances in the Study of Extracellular Vesicles in Colorectal Cancer.Gastroenterology · 2022Review
- A genetic model forOpen biology · 2022Article
- Epidermal growth factor/epidermal growth factor receptor signaling blockage inhibits tumor cell-derived exosome uptake by oral squamous cell carcinoma through macropinocytosis.Cancer science · 2022Article
- Pentapartite fractionation of particles in oral fluids by differential centrifugation.Scientific reports · 2021Article
- Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer.Cells · 2020Review
- Mechanisms of Action of EGFR Tyrosine Kinase Receptor Incorporated in Extracellular Vesicles.Cells · 2020Review
- Extracellular Vesicle-Dependent Cross-Talk in Cancer-Focus on Pancreatic Cancer.Frontiers in oncology · 2020Review
1 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
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Exosomes are small membrane vesicles derived from intracellular multivescicular bodies (MVBs) that can undergo constitutive and regulated secretion from cells. Exosomes can also secrete soluble proteins through metalloprotease-dependent ectodomain shedding. In this study, we sought to determine whether ErbB1 receptors are present within exosomes isolated from the human keratinocyte cell line, HaCaT, and whether exosome-associated ErbB1 receptors can undergo further proteolytic processing. We show that full-length transmembrane ErbB1 is secreted in HaCaT exosomes. EGF treatment and calcium flux stimulated the release of phosphorylated ErbB1 in exosomes but only ligand-stimulated release was blocked by the ErbB1 kinase inhibitor, AG1478, indicating that ligand-dependent ErbB1 receptor activation can initiate ErbB1 secretion into exosomes. In addition, other immunoreactive but truncated ErbB1 isoforms were detected in exosomes suggestive of additional proteolytic processing. We demonstrate that cellular and exosomal ErbB1 receptors can undergo ectodomain shedding to generate soluble N-terminal ectodomains and membrane-associated C-terminal remnant fragments (CTFs). ErbB1 shedding was activated by calcium flux and the metalloprotease activator APMA (4-aminophenylmercuric acetate) and was blocked by a metalloprotease inhibitor (GM6001). Soluble ErbB1 ectodomains shed into conditioned medium retained the ability to bind exogenous ligand. Our results provide new insights into the proteolysis, trafficking and fate of ErbB1 receptors and suggest that the novel ErbB1 isoforms may have functions distinct from the plasma membrane receptor.
Indexed as
Identifiers
What OpenQuestion holds
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.