ArticleInternational journal of cancer2019
Toll-like receptor 2 regulates metabolic reprogramming in gastric cancer via superoxide dismutase 2.
Article in International journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- Glycolysis‑driven immunosuppression in gastric cancer: Metabolic crosstalk between tumor cells and the immune microenvironment (Review).International journal of oncology · 2026Review
- Postbiotics From Ligilactobacillus salivarius Enhance Mitochondrial Robustness Via TLR2 Signaling in Intestinal Macrophages.Probiotics and antimicrobial proteins · 2026Article
- T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.Aging cell · 2026Review
- Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression.Free radical research · 2026Review
- The association between atopic dermatitis and rosacea: a comprehensive review from comorbidities to pathogenic mechanisms.Frontiers in immunology · 2026Review
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Targeting the MAPK signaling pathway: implications and prospects of flavonoids in 3P medicine as modulators of cancer cell plasticity and therapeutic resistance in breast cancer patients.The EPMA journal · 2025Article
- Effect of Maternal Probiotic and Piglet Dietary Tryptophan Level on Performance and Piglet Intestinal Health Parameters Pre-Weaning.Microorganisms · 2025Article
- Mechanisms and Recent Advances of Small-Molecule Therapeutics in Rosacea Treatment.Clinical, cosmetic and investigational dermatology · 2025Review
- Anti-proliferative and anti-invasive effects of exogenous thermostable MnSOD in gastric cancer associated with p53 and ZEB1 expression.Journal of Cancer · 2025Article
- Article
- Hypoxia-inducible factor-driven glycolytic adaptations in host-microbe interactions.Pflugers Archiv : European journal of physiology · 2024Review
- New Horizons in the Diagnosis of Gastric Cancer: The Importance of Selected Toll-like Receptors in Immunopathogenesis Depending on the Stage, Clinical Subtype, and Gender of Newly Diagnosed Patients.International journal of molecular sciences · 2024Article
- Cuproptosis-related gene DLAT is a biomarker of the prognosis and immune microenvironment of gastric cancer and affects the invasion and migration of cells.Cancer medicine · 2024Article
- Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis.World journal of gastrointestinal oncology · 2024Article
- Toll-like receptors in health and disease.MedComm · 2024Review
- Energy metabolism: a new target for gastric cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Treatment of rosacea with upadacitinib and abrocitinib: case report and review of evidence for Janus kinase inhibition in rosacea.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) play critical roles in host defense after recognition of conserved microbial- and host-derived components, and their dysregulation is a common feature of various inflammation-associated cancers, including gastric cancer (GC). Despite the recent recognition that metabolic reprogramming is a hallmark of cancer, the molecular effectors of altered metabolism during tumorigenesis remain unclear. Here, using bioenergetics function assays on human GC cells, we reveal that ligand-induced activation of TLR2, predominantly through TLR1/2 heterodimer, augments both oxidative phosphorylation (OXPHOS) and glycolysis, with a bias toward glycolytic activity. Notably, DNA microarray-based expression profiling of human cancer cells stimulated with TLR2 ligands demonstrated significant enrichment of gene-sets for oncogenic pathways previously implicated in metabolic regulation, including reactive oxygen species (ROS), p53 and Myc. Moreover, the redox gene encoding the manganese-dependent mitochondrial enzyme, superoxide dismutase (SOD)2, was strongly induced at the mRNA and protein levels by multiple signaling pathways downstream of TLR2, namely JAK-STAT3, JNK MAPK and NF-κB. Furthermore, siRNA-mediated suppression of SOD2 ameliorated the TLR2-induced metabolic shift in human GC cancer cells. Importantly, patient-derived tissue microarrays and bioinformatics interrogation of clinical datasets indicated that upregulated expression of TLR2 and SOD2 were significantly correlated in human GC, and the TLR2-SOD2 axis was associated with multiple clinical parameters of advanced stage disease, including distant metastasis, microvascular invasion and stage, as well as poor survival. Collectively, our findings reveal a novel TLR2-SOD2 axis as a potential biomarker for therapy and prognosis in cancer.
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Registered trials
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