ArticleJournal of cellular physiology2011
Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib.
Article in Journal of cellular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 177 citations in OpenAlex.
- Lipid Metabolism, Lipogenesis, and Resistance to Third Generation EGFR-TKIs.Journal of clinical laboratory analysis · 2026Review
- Protein-enhanced small molecule disruptors of ordered membrane domains.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lipids regulate epidermal growth factor receptor activation by its ligands.Biochemical Society transactions · 2026Review
- Pharmacological tools to modulate ordered membrane domains and order-dependent protein function.Communications chemistry · 2026Article
- Network pharmacology and molecular docking reveal mechanisms of amiodarone-induced pulmonary fibrosis.Scientific reports · 2026Article
- The role of statins in the treatment of lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: a protocol for systematic review and meta-analysis.Frontiers in medicine · 2026Article
- A Pseudomonas aeruginosa quorum-sensing inducer controls lung permeability in establishing chronic infection via EGFR.Nature communications · 2025Article
- Review
- Pharmacological Tools to Modulate Ordered Membrane Domains and Order-Dependent Protein Function.bioRxiv : the preprint server for biology · 2025Article
- Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics.Scientific reports · 2025Article
- Intracellular cholesterol: new functions and therapeutic approaches in NSCLC EGFR-TKI resistance.Lipids in health and disease · 2025Review
- Review
- Could serum Raftlin and GPER-1levels be new biomarkers for early detection of non-small cell lung cancer?Journal of cardiothoracic surgery · 2025Article
- Dual Receptor Targeting Ensures Uptake and Anticancer Efficacy of Low-Density Lipoprotein-Docosahexaenoic Acid Nanoparticles Across Breast Cancer Cell Subtypes.Breast cancer (Dove Medical Press) · 2025Article
- Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.bioRxiv : the preprint server for biology · 2024Article
- Loss of HD-PTP function results in lipodystrophy, defective cellular signaling and altered lipid homeostasis.Journal of cell science · 2024Article
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.Cancer discovery · 2024Article
- Cholesterol, Eukaryotic Lipid Domains, and an Evolutionary Perspective of Transmembrane Signaling.Cold Spring Harbor perspectives in biology · 2023Review
46 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is overexpressed in many cancer types including ~30% of breast cancers. Several small molecule tyrosine kinase inhibitors (TKIs) targeting EGFR have shown clinical efficacy in lung and colon cancers, but no benefit has been noted in breast cancer. Thirteen EGFR expressing breast cancer cell lines were analyzed for response to EGFR TKIs. Seven were found to be EGFR TKI resistant; while shRNA knockdown of EGFR determined that four of these cell lines retained the requirement of EGFR protein expression for growth. Interestingly, EGFR localized to plasma membrane lipid rafts in all four of these EGFR TKI-resistant cell lines, as determined by biochemical raft isolation and immunofluorescence. When lipid rafts were depleted of cholesterol using lovastatin, all four cell lines were sensitized to EGFR TKIs. In fact, the effects of the cholesterol biosynthesis inhibitors and gefitinib were synergistic. While gefitinib effectively abrogated phosphorylation of Akt- and mitogen-activated protein kinase in an EGFR TKI-sensitive cell line, phosphorylation of Akt persisted in two EGFR TKI-resistant cell lines, however, this phosphorylation was abrogated by lovastatin treatment. Thus, we have shown that lipid raft localization of EGFR correlates with resistance to EGFR TKI-induced growth inhibition and pharmacological depletion of cholesterol from lipid rafts decreases this resistance in breast cancer cell lines. Furthermore, we have presented evidence to suggest that when EGFR localizes to lipid rafts, these rafts provide a platform to facilitate activation of Akt signaling in the absence of EGFR kinase activity.
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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.