ArticleCellular and molecular life sciences : CMLS2021
Gefitinib induces EGFR and α5β1 integrin co-endocytosis in glioblastoma cells.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Programmed Cell Death Protein 10 (PDCD10) Regulates Vesicle Trafficking and Contributes to the Progression of Clear Cell Renal Cell Carcinoma.Journal of extracellular vesicles · 2025Article
- Application of EGFR-TKIs in brain tumors, a breakthrough in future?Journal of translational medicine · 2025Review
- Antagonism of epidermal growth factor receptor signaling favors hepatitis E virus life cycle.Journal of virology · 2024Article
- Review
- ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection.Life science alliance · 2023Article
- Glioblastoma multiforme: Diagnosis, treatment, and invasion.Journal of biomedical research · 2022Article
- Bioimaging Nucleic-Acid Aptamers with Different Specificities in Human Glioblastoma Tissues Highlights Tumoral Heterogeneity.Pharmaceutics · 2022Article
- The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics.Molecular therapy oncolytics · 2022Review
- ITGA5 Is a Novel Oncogenic Biomarker and Correlates With Tumor Immune Microenvironment in Gliomas.Frontiers in oncology · 2022Article
- Angiogenesis-Related Gene Signature-Derived Risk Score for Glioblastoma: Prospects for Predicting Prognosis and Immune Heterogeneity in Glioblastoma.Frontiers in cell and developmental biology · 2022Article
- Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.Frontiers in immunology · 2022Article
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- LncRNA NEAT1 Enhances Glioma Progression via Regulating the miR-128-3p/ITGA5 Axis.Molecular neurobiology · 2021Article
- Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells.Cancers · 2021Article
- Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Overexpression of EGFR drives glioblastomas (GBM) cell invasion but these tumours remain resistant to EGFR-targeted therapies such as tyrosine kinase inhibitors (TKIs). Endocytosis, an important modulator of EGFR function, is often dysregulated in glioma cells and is associated with therapy resistance. However, the impact of TKIs on EGFR endocytosis has never been examined in GBM cells. In the present study, we showed that gefitinib and other tyrosine kinase inhibitors induced EGFR accumulation in early-endosomes as a result of an increased endocytosis. Moreover, TKIs trigger early-endosome re-localization of another membrane receptor, the fibronectin receptor alpha5beta1 integrin, a promising therapeutic target in GBM that regulates physiological EGFR endocytosis and recycling in cancer cells. Super-resolution dSTORM imaging showed a close-proximity between beta1 integrin and EGFR in intracellular membrane compartments of gefitinib-treated cells, suggesting their potential interaction. Interestingly, integrin depletion delayed gefitinib-mediated EGFR endocytosis. Co-endocytosis of EGFR and alpha5beta1 integrin may alter glioma cell response to gefitinib. Using an in vitro model of glioma cell dissemination from spheroid, we showed that alpha5 integrin-depleted cells were more sensitive to TKIs than alpha5-expressing cells. This work provides evidence for the first time that EGFR TKIs can trigger massive EGFR and alpha5beta1 integrin co-endocytosis, which may modulate glioma cell invasiveness under therapeutic treatment.
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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.