ArticlePloS one2013
Overexpression of EGFR in head and neck squamous cell carcinoma is associated with inactivation of SH3GL2 and CDC25A genes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Prevalence of EGFR Tyrosine Kinase Domain Mutations in Head and Neck Squamous Cell Carcinoma: Cohort Study and Systematic Review.In vivo (Athens, Greece) · 2017Pooled it
- EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer.PloS one · 2018Trial
- Bending the boundaries: the many facets of endophilin-As from membrane dynamics to disease.Cellular and molecular life sciences : CMLS · 2025Review
- The microRNA-6510 as a potential tumor suppressor in head and neck cancer.Scientific reports · 2025Article
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- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- Targeted therapy based on ubiquitin-specific proteases, signalling pathways and E3 ligases in non-small-cell lung cancer.Frontiers in oncology · 2023Review
- Bioinformatics Analysis and Experimental Identification of Immune-Related Genes and Immune Cells in the Progression of Retinoblastoma.Investigative ophthalmology & visual science · 2022Article
- Exploring Degradation of Mutant and Wild-Type Epidermal Growth Factor Receptors Induced by Proteolysis-Targeting Chimeras.Journal of medicinal chemistry · 2022Article
- Article
- The prognostic impact of the immune signature in head and neck squamous cell carcinoma.Frontiers in immunology · 2022Article
- Evaluation of Methylation Profiles of An Epidermal Growth Factor Receptor Gene in a Head and Neck Squamous Cell Carcinoma Patient Group.Balkan journal of medical genetics : BJMG · 2020Article
- Cetuximab-Triptolide Conjugate Suppresses the Growth of EGFR-Overexpressing Lung Cancers through Targeting RNA Polymerase II.Molecular therapy oncolytics · 2020Article
- Downregulation of beta-catenin in chemo-tolerant TNBC through changes in receptor and antagonist profiles of the WNT pathway: Clinical and prognostic implications.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside.Current oncology reports · 2020Review
- Intron 1-Mediated Regulation ofMolecular cancer research : MCR · 2019Article
- Association of epidermal growth factor receptor protein expression with histopathological and clinical parameters in carcinoma of the larynx.Translational cancer research · 2019Article
- Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems.Pharmaceutics · 2019Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study is to understand the mechanism of EGFR overexpression in head and neck squamous cell carcinoma (HNSCC). For this reason, expression/mutation of EGFR were analyzed in 30 dysplastic head and neck lesions and 148 HNSCC samples of Indian patients along with 3 HNSCC cell lines. In addition, deletion/methylation/mutation/expression of SH3GL2 (associated with EGFR degradation) and CDC25A (associated with dephosphorylation of EGFR) were analyzed in the same set of samples. Our study revealed high frequency of EGFR overexpression (66-84%), low frequency of gene amplification (10-32.5%) and absence of functional mutation in the dysplastic lesions and HNSCC samples. No correlation was found between protein overexpression and mRNA expression/gene amplification status of EGFR. On the other hand, frequent alterations (deletion/methylation) of SH3GL2 (63-77%) and CDC25A (37-64%) were seen in the dysplastic and HNSCC samples. Two novel single nucleotide polymorphism (SNPs) were found in the promoter region of SH3GL2. Reduced expression of these genes showed concordance with their alterations. Overexpression of EGFR and p-EGFR were significantly associated with reduced expression and alterations of SH3GL2 and CDC25A respectively. In-vitro demethylation experiment by 5-aza-2'-deoxycytidine (5-aza-dC) showed upregulation of SH3GL2 and CDC25A and downregulation of EGFR expression in Hep2 cell line. Poor patient outcome was predicted in the cases with alterations of SH3GL2 and CDC25A in presence of human papilloma virus (HPV) infection. Also, low SH3GL2 and high EGFR expression was a predictor of poor patient survival. Thus, our data suggests that overexpression of EGFR due to its reduced degradation and dephosphorylation is needed for development of HNSCC.
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