ArticleCarcinogenesis2010
HIF-2alpha-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia.
Article in Carcinogenesis, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 54 citations in OpenAlex.
- A phase II study of tarloxotinib (a hypoxia activated prodrug of a pan-erb tyrosine kinase inhibitor) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or skin.Investigational new drugs · 2022Trial
- Expression of HIF-2α and VEGF in Cervical Squamous Cell Carcinoma and Its Clinical Significance.BioMed research international · 2016Trial
- Linking hypoxia-inducible factor (HIF)-1α and HIF-2α expression in head and neck cancer.Bioinformation · 2025Article
- Differential effects of hypoxia on motility using various in vitro models of lung adenocarcinoma.Scientific reports · 2024Article
- Tumor hypoxia and role of hypoxia-inducible factor in oral cancer.World journal of surgical oncology · 2024Review
- Regulation of epithelial-mesenchymal transition by tumor microenvironmental signals and its implication in cancer therapeutics.Seminars in cancer biology · 2023Review
- Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.Cancers · 2022Review
- Differential effects of HIF2α antagonist and HIF2α silencing in renal cancer and sensitivity to repurposed drugs.BMC cancer · 2021Article
- Review
- Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck.Frontiers in oncology · 2021Article
- Nicotine induces oral dysplastic keratinocyte migration via fatty acid synthase-dependent epidermal growth factor receptor activation.Experimental cell research · 2018Article
- Simultaneous targeting of EGFR, HER2, and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines.Molecular oncology · 2018Article
- Functional organic cation transporters mediate osteogenic response to metformin in human umbilical cord mesenchymal stromal cells.Cytotherapy · 2018Article
- Cell type-dependent HIF1 α-mediated effects of hypoxia on proliferation, migration and metastatic potential of human tumor cells.Oncotarget · 2017Article
- Downregulation of EGFR in hypoxic, diffusion-limited areas of squamous cell carcinomas of the head and neck.British journal of cancer · 2016Article
- Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2016Article
- HIF2α Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling.Cell metabolism · 2016Article
- Mechanisms of Invasion in Head and Neck Cancer.Archives of pathology & laboratory medicine · 2015Review
- Hypoxia modulates the activity of a series of clinically approved tyrosine kinase inhibitors.British journal of pharmacology · 2014Article
- Potential role of preoperative conventional MRI including diffusion measurements in assessing epidermal growth factor receptor gene amplification status in patients with glioblastoma.AJNR. American journal of neuroradiology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Despite their individual key roles in promoting head and neck squamous cell carcinoma (HNSCC) progression and treatment resistance, little is known about the impact of intratumoral hypoxia on the activity of the epidermal growth factor receptor (EGFR) signaling pathway in this cancer type. Here, we show that in highly EGFR-expressing HNSCC cells, hypoxic stress triggers the activation of the EGFR and downstream targets, including Akt and phospholipase C (PLC) gamma1. In support of these findings, we also demonstrate that EGFR activation takes place within hypoxic foci in a subset of human HNSCC tissues. Whereas hypoxia had no major effect on HNSCC cell proliferation, it markedly altered tumor cell shape by inducing morphological changes consistent with a more spindle-shaped, fibroblast-like morphology together with an enhanced migratory capacity. We found that hypoxia-induced EGFR activation and cell migration could be prevented by targeting EGFR signaling with the tyrosine kinase inhibitor tyrphostin, the phospholipase C inhibitor U73122, or by inhibiting the expression of the alpha subunit of hypoxia-inducible factor 2 via RNA interference or the topoisomerase II inhibitor etoposide. Our results position hypoxia-inducible factor-2alpha as a novel regulator of EGFR activation under low oxygen conditions, and suggest that hypoxia-induced EGFR signaling may promote a more aggressive phenotype in a fraction of HNSCC tumors. Because EGFR continues in the forefront as a highly attractive target in clinical oncology, further studies are warranted to define the mechanistic and therapeutic implications of the hypoxic response relative to the EGFR signaling pathway in head and neck cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.