ArticleLaboratory investigation; a journal of technical methods and pathology2022
The antioxidative stress regulator Nrf2 potentiates radioresistance of oral squamous cell carcinoma accompanied with metabolic modulation.
Article in Laboratory investigation; a journal of technical methods and pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- SMAD4 Expression and Its Association With Treatment Resistance and Clinical Outcomes in Oral Squamous Cell Carcinoma Treated With Preoperative Chemoradiotherapy.Cancer reports (Hoboken, N.J.) · 2026Article
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- Target choice and exon skipping regulate CRISPR-directed gene editing of NRF2 in head/neck and esophageal cancer cells.Molecular therapy. Oncology · 2026Article
- Mitochondrial-targeted therapeutics in oral squamous cell carcinoma: molecular and therapeutic implications.Frontiers in medicine · 2026Review
- Inflammation as a master regulator of immunotherapy response in head and neck squamous cell carcinoma: from malignant transformation to ecology-aware precision combinations.Frontiers in immunology · 2026Review
- Functional characterization of tumor-specific CRISPR-directed gene editing as a combinatorial therapy for the treatment of solid tumors.Molecular therapy. Oncology · 2025Article
- Nrf2 Drives Epigenetic Reprogramming and Acts as the Master Regulator of KLF4 Expression and Activity in Arsenic-Induced Transformation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interplay between Nrf2 and ROS in regulating epithelial-mesenchymal transition: implications for cancer metastasis and therapy.Molecular biology reports · 2025Review
- Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer.Cells · 2024Review
- Small molecules enhance the high-efficiency generation of pancreatic ductal organoids.Acta biochimica et biophysica Sinica · 2024Article
- Oxidative State in Cutaneous Melanoma Progression: A Question of Balance.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy.Biomedicines · 2024Article
- Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells.Redox biology · 2024Article
- Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma.Science advances · 2023Article
- The Effects of Umbilical Cord Mesenchymal Stem Cells -Derived Exosomes in Oral Squamous Cell Carcinoma (In vitro Study).Asian Pacific journal of cancer prevention : APJCP · 2023Article
- The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis.Molecules and cells · 2023Review
- Stimulation of Nuclear Factor (Erythroid-Derived 2)-like 2 Signaling by Nucleus Targeted Irradiation with Proton Microbeam.Biology · 2023Article
- Microbiota, Oxidative Stress, and Skin Cancer: An Unexpected Triangle.Antioxidants (Basel, Switzerland) · 2023Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
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Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of critical antioxidant proteins, was recently demonstrated to play a key role in cancer progression. Resistance to radiotherapy is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about the association between Nrf2 and radioresistance in OSCC. Two OSCC cell lines (SAS and HSC-2) and their clinically relevant radioresistant (CRR) clones (SAS-R, HSC-2-R) were used. The effects of Nrf2 downregulation on radiosensitivity and the involvement of glycolysis in Nrf2-mediated radioresistance were evaluated. Immunohistochemistry of phosphorylated Nrf2 (p-Nrf2) was performed in 110 patients with OSCC who underwent preoperative chemoradiotherapy and surgery. Nrf2 was stably upregulated in CRR cells in vitro and in a mouse xenograft model. Moreover, elevated Nrf2 expression was associated with radioresistance. The enhancement of Nrf2-dependent glycolysis and glutathione synthesis was involved in the development of radioresistance. Additionally, p-Nrf2 expression was closely related to the pathological response to chemoradiotherapy, and its expression was predictive of prognosis in patients with advanced OSCC. Our results suggest that Nrf2 plays an important role in the radioresistance of OSCC accompanied by metabolic reprogramming. Targeting Nrf2 antioxidant pathway may represent a promising treatment strategy for highly malignant OSCC.
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