ArticleCancer science2023
Ligand-independent EphA2 contributes to chemoresistance in small-cell lung cancer by enhancing PRMT1-mediated SOX2 methylation.
Article in Cancer science, 2023. 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, 25 citations in OpenAlex.
- Dysregulated mScience advances · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Targeting the PRMT1 axis in cancer: from epigenetic plasticity to contextual therapeutic interventions.Frontiers in oncology · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- PRMT1 in Health and Disease: Emerging Perspectives From Molecular Mechanisms to Therapeutic Strategies.MedComm · 2025Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Immunotherapy for small cell lung cancer: current challenges and prospects.Experimental hematology & oncology · 2025Review
- Dual-Action Tocilizumab-Conjugated Cisplatin Nanoparticles Overcome Chemoresistance and Metastasis in Non-Small-Cell Lung Cancer.Pharmaceutics · 2025Article
- Arginine methylation patterns in LUAD: defining prognostic subtypes and relevance to immunotherapy.Discover oncology · 2025Article
- A DNA Nanomachine Modulates the Stemness-Associated Signaling Pathways for Overcoming Chemoresistance by Temporally Programming Drug Release.Research (Washington, D.C.) · 2025Article
- EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Review
- Unraveling the role of EPHA2 in regulating migration and immunomodulation processes in cervical cancer: exploring the synergic effect of 17β-estradiol on cancer progression.Medical oncology (Northwood, London, England) · 2024Article
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer.Molecular cancer · 2024Review
- PRMT1 in human neoplasm: cancer biology and potential therapeutic target.Cell communication and signaling : CCS · 2024Review
- Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer.Scientific reports · 2024Article
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Hypoxia-induced TGFBI maintains glioma stem cells by stabilizing EphA2.Theranostics · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Chemoresistance is the crux of clinical treatment failure of small-cell lung cancer (SCLC). Cancer stem cells play a critical role in therapeutic resistance of malignant tumors. Studies have shown that the role of erythropoietin-producing hepatocellular A2 (EphA2) in tumors is complex. This study aimed to test the hypothesis that ligand-independent activation of EphA2 modulates chemoresistance by enhancing stemness in SCLC. We verified that EphA2 was activated in chemoresistance sublines in a ligand-independent manner rather than a ligand-dependent manner. Ligand-independent EphA2 enhanced the expression of stemness-associated biomarkers (CD44, Myc, and SOX2), accelerated epithelial-mesenchymal transition (EMT) and reinforced self-renewal to drive the chemoresistance of SCLC, while the P817H mutant EphA2 neutralized intrinsic function. Co-immunoprecipitation (co-IP) and GST-pull down experiments were conducted to verify that EphA2 directly interacted with PRMT1. Moreover, EphA2 increased the expression and activity of PRMT1. Whereafter, PRMT1 interacted with and methylated SOX2 to induce stemness and chemoresistance in SCLC. Pharmacological inhibition of EphA2 showed a synergistic anti-tumor effect with chemotherapy in preclinical models, including patient-derived xenograft (PDX) models. These findings highlight, for the first time, that the EphA2/PRMT1/SOX2 pathway induces chemoresistance in SCLC by promoting stemness. EphA2 is a potential therapeutic target in SCLC treatment.
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Registered trials
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.