ArticleThe Journal of cell biology2001
EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion.
Article in The Journal of cell biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 305 citations in OpenAlex.
- Enhancing the Potency of Growth Factor-Mimicking Peptides via Cross-Presentation With Integrin Ligands.Journal of biomedical materials research. Part A · 2025Article
- Acetylation-dependent coupling between G6PD activity and apoptotic signaling.Nature communications · 2023Article
- Revising the Role of Integrin Subunit β4 Expression in Colon Cancer Progression and Survival.Journal of gastrointestinal cancer · 2023Article
- KCNF1 promotes lung cancer by modulating ITGB4 expression.Cancer gene therapy · 2023Article
- Tau differentially regulates the transport of early endosomes and lysosomes.Molecular biology of the cell · 2022Article
- Plasma membrane proteoglycans syndecan-2 and syndecan-4 engage with EGFR and RON kinase to sustain carcinoma cell cycle progression.The Journal of biological chemistry · 2022Article
- c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.Frontiers in cell and developmental biology · 2022Review
- Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action.Clinical, cosmetic and investigational dermatology · 2022Review
- The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis.International journal of molecular sciences · 2021Review
- EGFR-dependent tyrosine phosphorylation of integrin β4 is not required for downstream signaling events in cancer cell lines.Scientific reports · 2021Article
- Phenotypic Plasticity of Cancer Cells Based on Remodeling of the Actin Cytoskeleton and Adhesive Structures.International journal of molecular sciences · 2021Review
- Syndecans and Their Synstatins: Targeting an Organizer of Receptor Tyrosine Kinase Signaling at the Cell-Matrix Interface.Frontiers in oncology · 2021Review
- The roles of integrins in cancer.Faculty reviews · 2021Review
- EGFR-Dependent Extracellular Matrix Protein Interactions Might Light a Candle in Cell Behavior of Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Review
- Interplay between Cell-Surface Receptors and Extracellular Matrix in Skin.Biomolecules · 2020Review
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- The Specificity of EGF-Stimulated IQGAP1 Scaffold Towards the PI3K-Akt Pathway is Defined by the IQ3 motif.Scientific reports · 2019Article
- Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer.Cancers · 2019Review
- Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance.Cancer cell · 2019Review
62 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We have examined the mechanism and functional significance of hemidesmosome disassembly during normal epithelial cell migration and squamous carcinoma invasion. Our findings indicate that a fraction of EGF receptor (EGF-R) combines with the hemidesmosomal integrin alpha6beta4 in both normal and neoplastic keratinocytes. Activation of the EGF-R causes tyrosine phosphorylation of the beta4 cytoplasmic domain and disruption of hemidesmosomes. The Src family kinase inhibitors PP1 and PP2 prevent tyrosine phosphorylation of beta4 and disassembly of hemidesmosomes without interfering with the activation of EGF-R. Coimmunoprecipitation experiments indicate that Fyn and, to a lesser extent, Yes combine with alpha6beta4. By contrast, Src and Lck do not associate with alpha6beta4 to a significant extent. A dominant negative form of Fyn, but not Src, prevents tyrosine phosphorylation of beta4 and disassembly of hemidesmosomes. These observations suggest that the EGF-R causes disassembly of hemidesmosomes by activating Fyn, which in turn phosphorylates the beta4 cytoplasmic domain. Neoplastic cells expressing dominant negative Fyn display increased hemidesmosomes and migrate poorly in vitro in response to EGF. Furthermore, dominant negative Fyn decreases the ability of squamous carcinoma cells to invade through Matrigel in vitro and to form lung metastases following intravenous injection in nude mice. These results suggest that disruption of hemidesmosomes mediated by Fyn is a prerequisite for normal keratinocyte migration and squamous carcinoma invasion.
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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.