ArticleNeoplasia (New York, N.Y.)2025
EGFRvIII-driven microenvironmental fibroblast activation and transformation accelerate oral cancer progression via lipocalin-2/STAT3 axis.
Article in Neoplasia (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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.
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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.
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Who cites it
2 citing papers in PubMed.
- PDIA3 Inhibition Facilitates Sensitivity of IKE-Induced Ferroptosis via STAT3/LCN2 Axis to Improve Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- EGFRvIII expression in head and neck squamous cell carcinoma: clinical significance and sources of frequency variation across studies.Frontiers in oncology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy frequently characterized by dysregulated epidermal growth factor receptor (EGFR) signaling. Among EGFR mutation, EGFRvIII, an extracellular domain truncated form without exons 2-7, exhibits ligand-independent and constitutive EGFR activation. Although EGFRvIII functions as an oncogene in glioblastoma, its role in OSCC remains unclear. Here, we demonstrate that EGFRvIII is highly prevalent in OSCC, with approximately 70 % of OSCC tumor samples revealing high EGFRvIII expression. EGFRvIII enhances metastatic and proliferative potential, while its knockdown significantly reduces these malignant phenotypes. Beyond its direct oncogenic effects, EGFRvIII actively remodels the tumor microenvironment (TME) by recruiting and activating fibroblasts. In both xenograft models and co-culture systems, OSCC cells expressing EGFRvIII stimulated the expression of fibroblast activation markers-including α-smooth muscle actin (α-SMA), platelet-derived growth factor receptors (PDGFRA/PDGFRB), and collagen-thereby promoting a tumor-supportive stroma. Moreover, RNA sequencing and cytokine array analyses revealed that EGFRvIII induces lipocalin-2 (LCN2) expression and secretion. Elevated LCN2 in the conditioned medium from OSCC-EGFRvIII cells further stimulates fibroblast activation via the STAT3 signaling pathway, as pharmacological inhibition of STAT3 attenuates LCN2-driven fibroblast activation. Furthermore, exposure to environmental carcinogens such as nicotine-derived nitrosamine ketone (NNK) and arecoline enhances EGFRvIII expression and downstream signaling, exacerbating tumor aggressiveness. These findings reveal a positive feedback loop in which EGFRvIII fosters OSCC progression by stimulating LCN2-STAT3-mediated fibroblast activation. Targeting EGFRvIII and its downstream effectors may therefore represent a promising strategy to mitigate OSCC progression and improve therapeutic outcomes.
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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 Socratic graph.