ArticleProceedings of the National Academy of Sciences of the United States of America2007
Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 278 citations in OpenAlex.
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Oxygen-carrying nanovaccine potentiates cancer immunotherapy for heterogeneous solid tumors.Materials today. Bio · 2026Article
- LncRNA EUDAL shapes tumor cell response to hypoxia-induced constitutive EGFR activation and promotes chemoresistance in oral cancer.International journal of oral science · 2025Article
- The Binding Affinities of Serum Proteins to Nanoparticles.Journal of the American Chemical Society · 2025Article
- Design and investigation of novel iridoid-based peptide conjugates for targeting EGFR and its mutants L858R and T790M/L858R/C797S: an in silico study.Molecular diversity · 2025Article
- Loss of VHL-mediated pRb regulation promotes clear cell renal cell carcinoma.Cell death & disease · 2025Article
- FDX1 Regulates the Phosphorylation of ATM, DNA-PKcs Akt, and EGFR and Affects Radioresistance Under Severe Hypoxia in the Glioblastoma Cell Line T98G.International journal of molecular sciences · 2025Article
- Article
- Cargo-specific effects of hypoxia on clathrin-mediated trafficking.Pflugers Archiv : European journal of physiology · 2024Article
- The Evolving Paradigm of Antibody-Drug Conjugates Targeting the ErbB/HER Family of Receptor Tyrosine Kinases.Pharmaceutics · 2024Review
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer.Frontiers in oncology · 2024Article
- Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.Molecular imaging and biology · 2023Review
- Enzyme-triggered deep tumor penetration of a dual-drug nanomedicine enables an enhanced cancer combination therapy.Bioactive materials · 2023Article
- MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.Cancer communications (London, England) · 2023Article
- Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- ErbB signaling is a potential therapeutic target for vascular lesions with fibrous component.eLife · 2023Article
- Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.Cancers · 2023Review
- Antibody drug conjugates, targeting cancer-expressed EGFR, exhibit potent and specific antitumor activity.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- A new paradigm for epidermal growth factor receptor expression exists in PTC and NIFTP regulated by microRNAs.Frontiers in oncology · 2023Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of the EGF receptor (EGFR) is a recurrent theme in human cancer and is thought to cause aggressive phenotypes and resistance to standard therapy. There has, thus, been a concerted effort in identifying EGFR gene mutations to explain misregulation of EGFR expression as well as differential sensitivity to anti-EGFR drugs. However, such genetic alterations have proven to be rare occurrences in most types of cancer, suggesting the existence of a more general physiological trigger for aberrant EGFR expression. Here, we provide evidence that overexpression of wild-type EGFR can be induced by the hypoxic microenvironment and activation of hypoxia-inducible factor 2-alpha (HIF2alpha) in the core of solid tumors. Our data suggest that hypoxia/HIF2alpha activation represents a common mechanism for EGFR overexpression by increasing EGFR mRNA translation, thereby diminishing the necessity for gene mutations. This allows for the accumulation of elevated EGFR levels, increasing its availability for the autocrine signaling required for tumor cell growth autonomy. Taken together, our findings provide a nonmutational explanation for EGFR overexpression in human tumors and highlight a role for HIF2alpha activation in the regulation of EGFR protein synthesis.
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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.