ArticleJournal of experimental & clinical cancer research : CR2023
Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Experimental Models and Nanotechnology-Based Platforms in Oral Squamous Cell Carcinoma: From Tumor Biology to Translational Applications.Pharmaceutics · 2026Review
- Shared Biomarkers LCN2 and CXCL11 for Ulcerative Colitis and Colon Cancer: Bioinformatics Analysis and Diagnostic Model Construction.Digestive diseases and sciences · 2026Article
- Mechanisms of astragalus polysaccharide enhancing STM2457 therapeutic efficacy in mMedical oncology (Northwood, London, England) · 2026Article
- Key Early Changes in Oral Squamous Cell Carcinogenesis Are Accelerated by Ectopic BMI1 Expression.Cancer research communications · 2026Article
- HDAC1 Regulates Acquired Resistance to EGFR Inhibitors through the TFCP2-NDRG1 Signaling Axis in Pancreatic Cancer.International journal of biological sciences · 2026Article
- Dissecting the role of epigenetic regulation in oral squamous cell carcinoma microenvironment: mechanisms and therapeutics.Frontiers in immunology · 2026Review
- KLHL4 upregulates EGFR signaling to promote the malignant progression of oral squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2025Article
- LCP1 upregulation via EGFR signaling promotes oral cancer progression through the JAK2/STAT3/IL-1β axis.Cancer cell international · 2025Article
- Evolving role of deubiquitinating enzymes in oral cancer (Review).Oncology letters · 2025Review
- Neoadjuvant Chemotherapy With Cisplatin Up-Regulates GSDMD to Enhance Oral Squamous Cell Carcinoma Metastasis Through MMP14-Mediated EMT Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LCN2 promotes focal adhesion formation and invasion by stimulating c-Src activation.Journal of cell science · 2025Article
- Lipocalin-2 promotes NSCLC progression by activating the JAK2/STAT3 signaling pathway.Journal of translational medicine · 2025Article
- BMP2 expression in oral squamous cell carcinoma and its effects on SCC9 cell biological behavior.Scientific reports · 2025Article
- Exogenous BMI1 expression aggravates oral squamous cell carcinomas in tongue epithelia.Neoplasia (New York, N.Y.) · 2025Article
- Article
- Oncogenic and tumor-suppressive roles of Lipocalin 2 (LCN2) in tumor progression.Oncology research · 2025Review
- Metabolic biomarker in oral squamous cell carcinoma - a comprehensive review.GMS Interdisciplinary plastic and reconstructive surgery DGPW · 2025Review
- Reduction-responsive RNAi nanoplatform for enhanced cancer sonoimmunotherapy via dual inhibition of mitophagy and Nrf2 pathways.Theranostics · 2025Article
- Roles of intralesional bacteria in the initiation and progression of oral squamous cell carcinoma.Cancer medicine · 2024Review
- Leveraging the intratumoral microbiota to treat human cancer: are engineered exosomes an effective strategy?Journal of translational medicine · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEGFR is an important signal involved in tumor growth that can induce tumor metastasis and drug resistance. Exploring targets for effective EGFR regulation is an important topic in current research and drug development. Inhibiting EGFR can effectively inhibit the progression and lymph node metastasis of oral squamous cell carcinoma (OSCC) because OSCC is a type of cancer with high EGFR expression. However, the problem of EGFR drug resistance is particularly prominent, and identifying a new target for EGFR regulation could reveal an effective strategy.
methodsWe sequenced wild type or EGFR-resistant OSCC cells and samples from OSCC patients with or without lymph node metastasis to find new targets for EGFR regulation to effectively replace the strategy of directly inhibiting EGFR and exert an antitumor effect. We then investigated the effect of LCN2 on OSCC biological abilities in vitro and in vivo through protein expression regulation. Subsequently, we elucidated the regulatory mechanism of LCN2 through mass spectrometry, protein interaction, immunoblotting, and immunofluorescence analyses. As a proof of concept, a reduction-responsive nanoparticle (NP) platform was engineered for effective LCN2 siRNA (siLCN2) delivery, and a tongue orthotopic xenograft model as well as an EGFR-positive patient-derived xenograft (PDX) model were applied to investigate the curative effect of siLCN2.
resultsWe identified lipocalin-2 (LCN2), which is upregulated in OSCC metastasis and EGFR resistance. Inhibition of LCN2 expression can effectively inhibit the proliferation and metastasis of OSCC in vitro and in vivo by inhibiting EGFR phosphorylation and downstream signal activation. Mechanistically, LCN2 binds EGFR and enhances the recycling of EGFR, thereby activating the EGFR-MEK-ERK cascade. Inhibition of LCN2 effectively inhibited the activation of EGFR. We translated this finding by systemic delivery of siLCN2 by NPs, which effectively downregulated LCN2 in the tumor tissues, thereby leading to a significant inhibition of the growth and metastasis of xenografts.
conclusionsThis research indicated that targeting LCN2 could be a promising strategy for the treatment of OSCC.
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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.