ArticleJCI insight2023
EGFR inhibition leads to enhanced desmosome assembly and cardiomyocyte cohesion via ROCK activation.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- RhoGEF Ect2 supports RhoA activity at cell-cell junctions through desmoplakin.Life science alliance · 2026Article
- Transcriptome-Based Analysis of Core Hub Genes Related to Cell Adhesion in Vero Cells.BioMed research international · 2026Article
- Apremilast improves cardiomyocyte cohesion and arrhythmia in different models for arrhythmogenic cardiomyopathy.Stem cell research & therapy · 2025Article
- Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.Journal of cell science · 2025Article
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.The Journal of cell biology · 2024Article
- DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts.Nature communications · 2024Article
- Cardiomyocyte cohesion is increased after ADAM17 inhibition.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arrhythmogenic cardiomyopathy (AC) is a familial heart disease partly caused by impaired desmosome turnover. Thus, stabilization of desmosome integrity may provide new treatment options. Desmosomes, apart from cellular cohesion, provide the structural framework of a signaling hub. Here, we investigated the role of the epidermal growth factor receptor (EGFR) in cardiomyocyte cohesion. We inhibited EGFR under physiological and pathophysiological conditions using the murine plakoglobin-KO AC model, in which EGFR was upregulated. EGFR inhibition enhanced cardiomyocyte cohesion. Immunoprecipitation showed an interaction of EGFR and desmoglein 2 (DSG2). Immunostaining and atomic force microscopy (AFM) revealed enhanced DSG2 localization and binding at cell borders upon EGFR inhibition. Enhanced area composita length and desmosome assembly were observed upon EGFR inhibition, confirmed by enhanced DSG2 and desmoplakin (DP) recruitment to cell borders. PamGene Kinase assay performed in HL-1 cardiomyocytes treated with erlotinib, an EGFR inhibitor, revealed upregulation of Rho-associated protein kinase (ROCK). Erlotinib-mediated desmosome assembly and cardiomyocyte cohesion were abolished upon ROCK inhibition. Thus, inhibiting EGFR and, thereby, stabilizing desmosome integrity via ROCK might provide treatment options for AC.
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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.