ArticleCancer science2021
N-glycosylated GPNMB ligand independently activates mutated EGFR signaling and promotes metastasis in NSCLC.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Integrative Proteomic and Metabolomic Analyses Reveal Arginase-1-Mediated Nitrogen Metabolic Reprogramming Associated with Growth Advantage in Ronglai Binary Hybrid Pigs.Animals : an open access journal from MDPI · 2026Article
- GPNMB regulates EGFR mitochondrial translocation via HK2, influencing microglial respiratory chain and metabolic defects to promote polarization and stroke progression.Cell biology and toxicology · 2026Article
- GPNMB-ECD drives acquired resistance to osimertinib in NSCLC via inducing tumor cell cytoskeletal reorganization.Cellular & molecular biology letters · 2026Article
- Integrative structural and dynamics studies of epidermal growth factor receptor (EGFR).Experimental & molecular medicine · 2026Review
- Therapeutic targeting of cancer stem cell-specific surface glycans and glycoproteins.Discover oncology · 2026Review
- GPNMB disrupts SNARE complex assembly to maintain bacterial proliferation within macrophages.Cellular & molecular immunology · 2025Article
- MSC-sEVs exacerbate senescence by transferring bisecting GlcNAcylated GPNMB.Stem cell research & therapy · 2025Article
- Post-translational modifications of protein and lung cancer.Frontiers in oncology · 2025Review
- Identification of GPNMB in endometrial cancer based on pan-cancer analysis and in vitro validation.Discover oncology · 2024Article
- GPNMB Expression Associates with Inferior Prognosis in Patients with Small Cell Lung Cancer.Journal of Cancer · 2024Article
- Diverse perspectives on proteomic posttranslational modifications to address EGFR-TKI resistance in non-small cell lung cancer.Frontiers in cell and developmental biology · 2024Review
- Variant Analysis of miRNA Regulatory Genes in 35 Sporadic Lung Carcinoma Tumors.Doklady. Biochemistry and biophysics · 2023Article
- Single-cell transcriptome sequencing-based analysis: probing the mechanisms of glycoprotein NMB regulation of epithelial cells involved in silicosis.Particle and fibre toxicology · 2023Article
- Human Antibody VMolecular pharmaceutics · 2023Article
- Human Papillomavirus Infection andJournal of personalized medicine · 2023Article
- Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation.Open medicine (Warsaw, Poland) · 2023Article
- Prognostic Value of GPNMB, EGFR, p-PI3K, and Ki-67 in Patients with Esophageal Squamous Cell Carcinoma.Analytical cellular pathology (Amsterdam) · 2022Article
- Abnormal sialylation and fucosylation of saliva glycoproteins: Characteristics of lung cancer-specific biomarkers.Current research in pharmacology and drug discovery · 2022Review
- N-glycosylated GPNMB ligand independently activates mutated EGFR signaling and promotes metastasis in NSCLC.Cancer science · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. As well as the identified role of epidermal growth factor receptor (EGFR), its association with driver mutations has improved the therapeutics for patients with lung cancer harboring EGFR mutations. These patients usually display shorter overall survival and a higher tendency to develop distant metastasis compared with those carrying the wild-type EGFR. Nevertheless, the way to control mutated EGFR signaling remains unclear. Here, we performed membrane proteomic analysis to determine potential components that may act with EGFR mutations to promote lung cancer malignancy. Expression of transmembrane glycoprotein non-metastatic melanoma protein B (GPNMB) was positively correlated with the status of mutated EGFR in non-small-cell lung cancer (NSCLC). This protein was not only overexpressed but also highly glycosylated in EGFR-mutated, especially EGFR-L858R mutated, NSCLC cells. Further examination showed that GPNMB could activate mutated EGFR without ligand stimulation and could bind to the C-terminus of EGFR, assist phosphorylation at Y845, turn on downstream STAT3 signaling, and promote cancer metastasis. Moreover, we also found that Asn134 (N134) glycosylation of GPNMB played a crucial role in this ligand-independent regulation. Depleting N134-glycosylation on GPNMB could dramatically inhibit binding of GPNMB to mutated EGFR, blocking its downstream signaling, and ultimately inhibiting cancer metastasis in NSCLC. Clarifying the role of N-glycosylated GPNMB in regulating the ligand-independent activation of mutated EGFR may soon give new insight into the development of novel therapeutics for NSCLC.
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