ArticleNature communications2024
Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Senescent tumor cell membrane-based "time engine" nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade.Science advances · 2026Article
- Overexpression of human interleukin 6 in NaCl inducible bacterial system and its characterization.Applied biochemistry and biotechnology · 2026Article
- Distinct glycosyltransferase expression governs organ-specific survival in pancreatic cancer metastasis.Oncogene · 2026Article
- Optimized Simultaneous N/O-Glycopeptide Enrichment Strategy Identifies Lung Cancer Diagnostic Biomarkers in Serum.Journal of proteome research · 2026Article
- Glucose deprivation drives LIF-dependent lung cancer.Nature metabolism · 2026Article
- METTL14 modulates the nasopharyngeal carcinoma microenvironment via mFrontiers in immunology · 2026Article
- Integrative Analysis of Glycosylation-Related Genes Reveals Prognostic Subtypes, Immune Evasion, and Therapeutic Vulnerabilities in Lung Adenocarcinoma.Oncology research · 2026Article
- Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance.Frontiers in cell and developmental biology · 2026Article
- Advancing the understanding of the role of apoptosis in lung cancer immunotherapy: Global research trends, key themes, and emerging frontiers.Human vaccines & immunotherapeutics · 2025Article
- METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells.Cancer medicine · 2025Article
- Review
- Next-generation protein sequencing and individual ion mass spectrometry enable complementary analysis of interleukin-6.Analytical and bioanalytical chemistry · 2025Article
- [Research Progress on Interleukin-6 in Screening and Prognosis of Patients with Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Nordihydroguaiaretic acid inhibits bladder cancer metastasis through suppression of α1,3-mannosyltransferase expression and LRFN4 N-glycosylation.Journal of translational medicine · 2025Article
- Hotspots and frontiers of extracellular vesicles and lung cancer: a bibliometric and visualization analysis from 2002 to 2024.Discover oncology · 2025Article
- The biology of interleukin-6 family cytokines is regulated by glycosylation.The Biochemical journal · 2025Review
- Influence of interleukin-6 on the pharmacokinetics and pharmacodynamics of osimertinib in patients with non-small cell lung cancer.Cancer chemotherapy and pharmacology · 2025Article
- Review
- Anlotinib enhances the anti-tumor activity of osimertinib in patients with non-small cell lung cancer by reversing drug resistance.Translational lung cancer research · 2025Article
- Global research trends and emerging hotspots in nano-drug delivery systems for lung cancer: a comprehensive bibliometric analysis (1998-2024).Discover oncology · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein find that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induces epithelial-mesenchymal transition (EMT) and migration in vitro and metastasis in vivo, which are suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secrete a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution.
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