ArticleOncogene2010
Epidermal growth factor receptor regulates MET levels and invasiveness through hypoxia-inducible factor-1alpha in non-small cell lung cancer cells.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 94 citations in OpenAlex.
- Trial
- A Phase Ib/II Study of Ramucirumab in Combination with Emibetuzumab in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- MEN1-Related Neuroendocrine Tumors Show c-MET Overexpression.Journal of the Endocrine Society · 2025Article
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The expanding role of the receptor tyrosine kinase MET as a therapeutic target in non-small cell lung cancer.Cell reports. Medicine · 2025Review
- Efficacy and prognostic analysis of chemo-immunotherapy after TKI resistance in EGFR-mutant non-small cell lung cancer with TP53 or KRAS co-mutations.Frontiers in immunology · 2025Article
- HIF-1α-HPRT1 axis promotes tumorigenesis and gefitinib resistance by enhancing purine metabolism in EGFR-mutant lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Overcoming EGFR-TKI resistance by targeting the tumor microenvironment.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Molecular basis of VEGFR1 autoinhibition at the plasma membrane.Nature communications · 2024Article
- The Nail in the Coffin?: Examining the KEYNOTE-789 Clinical Trial's Impact.Lung Cancer (Auckland, N.Z.) · 2024Article
- Outcome benefits of bevacizumab biosimilar (SIBP04) combined with carboplatin and paclitaxel in advanced non-squamous non-small-cell lung cancer patients with EGFR mutation: subgroup analysis of a prospective, randomized phase III clinical trial.Journal of cancer research and clinical oncology · 2023Article
- Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance.Japanese journal of clinical oncology · 2023Review
- IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?Healthcare (Basel, Switzerland) · 2023Article
- Molecular Mechanisms and Future Implications of VEGF/VEGFR in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Research advances in mechanism of antiangiogenic therapy combined with immune checkpoint inhibitors for treatment of non-small cell lung cancer.Frontiers in immunology · 2023Review
- Tumor vessel co-option: The past & the future.Frontiers in oncology · 2022Review
- Osimertinib: Another medication related to osteonecrosis of the jaws? A case report and literature review.Frontiers in pharmacology · 2022Article
- Estrogen Promotes Resistance to Bevacizumab in Murine Models of NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021Article
- Review
2 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
19 authors at 3 institutions in 1 country.
Funding
Abstract
Recent studies have established that amplification of the MET proto-oncogene can cause resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) cell lines with EGFR-activating mutations. The role of non-amplified MET in EGFR-dependent signaling before TKI resistance, however, is not well understood. Using NSCLC cell lines and transgenic models, we demonstrate here that EGFR activation by either mutation or ligand binding increases MET gene expression and protein levels. Our analysis of 202 NSCLC patient specimens was consistent with these observations: levels of MET were significantly higher in NSCLC with EGFR mutations than in NSCLC with wild-type EGFR. EGFR regulation of MET levels in cell lines occurred through the hypoxia-inducible factor (HIF)-1alpha pathway in a hypoxia-independent manner. This regulation was lost, however, after MET gene amplification or overexpression of a constitutively active form of HIF-1alpha. EGFR- and hypoxia-induced invasiveness of NSCLC cells, but not cell survival, were found to be MET dependent. These findings establish that, absent MET amplification, EGFR signaling can regulate MET levels through HIF-1alpha and that MET is a key downstream mediator of EGFR-induced invasiveness in EGFR-dependent NSCLC cells.
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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.