ArticleOncogene2022
Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Vesicles for cell crosstalk in bone: composition, function and application.Science China. Life sciences · 2026Review
- Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells.Cancer letters · 2026Article
- Novel therapeutic strategies for targeting fatty acid oxidation in cancer.Biomarker research · 2025Review
- Integrated Microfluidic Chip for Neutrophil Extracellular Vesicle Analysis and Gastric Cancer Diagnosis.ACS nano · 2025Article
- Ambivalent roles of miRNAs in cancer development via modulating tumor-associated innate immune cells.BioImpacts : BI · 2025Review
- The miR-941/FOXN4/TGF-β feedback loop induces N2 polarization of neutrophils and enhances tumor progression of lung adenocarcinoma.Frontiers in immunology · 2025Article
- Effects of particulate air pollution exposure on lung-brain axis and related miRNAs modulation in mouse models.Frontiers in cell and developmental biology · 2025Review
- MicroRNA in pediatric pulmonary hypertension microRNA profiling to inform disease classification, severity, and treatment response in pediatric pulmonary hypertension.American journal of physiology. Heart and circulatory physiology · 2025Article
- Exosome tropism and various pathways in lung cancer metastasis.Frontiers in immunology · 2025Review
- Review
- Review
- MiR-21-3p inhibitor exerts myocardial protective effects by altering macrophage polarization state and reducing excessive mitophagy.Communications biology · 2024Article
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Exosomal miR-4745-5p/3911 from N2-polarized tumor-associated neutrophils promotes gastric cancer metastasis by regulating SLIT2.Molecular cancer · 2024Article
- Recent advances to address challenges in extracellular vesicle-based applications for lung cancer.Acta pharmaceutica Sinica. B · 2024Review
- CBX4/miR-190 regulatory loop inhibits lung cancer metastasis.Thoracic cancer · 2024Article
- Review
- Exosomal miRNAs: the tumor's trojan horse in selective metastasis.Molecular cancer · 2024Review
- Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6.Cell death discovery · 2024Article
- α5-nAChR/ADAM10 signaling mediates nicotine-related cutaneous melanoma progression via STAT3 activation.Archives of dermatological research · 2024Article
Corrections and comments
- Retraction · 2025-01-09Concerns/Issues about Image · Duplication of/in Image · Euphemisms for Duplication · · see also: https://pubpeer.com/publications/B5C4BF50D0A1F667956AD5E182D801
- Retracted
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Smoking is associated with lung cancer and has a profound impact on tumor immunity. Nicotine, the addictive and non-carcinogenic smoke component, influences various brain cells and the immune system. However, how long-term use of nicotine affects brain metastases is poorly understood. We, therefore, examined the mechanism by which nicotine promotes lung cancer brain metastasis. In this study, we conducted a retrospective analysis of 810 lung cancer patients with smoking history and assessed brain metastasis. We found that current smoker's lung cancer patients have significantly higher brain metastatic incidence compared to the never smokers. We also found that chronic nicotine exposure recruited STAT3-activated N2-neutrophils within the brain pre-metastatic niche and secreted exosomal miR-4466 which promoted stemness and metabolic switching via SKI/SOX2/CPT1A axis in the tumor cells in the brain thereby enabling metastasis. Importantly, exosomal miR-4466 levels were found to be elevated in serum/urine of cancer-free subjects with a smoking history and promote tumor growth in vivo, suggesting that exosomal miR-4466 may serve as a promising prognostic biomarker for predicting increased risk of metastatic disease among smoker(s). Our findings suggest a novel pro-metastatic role of nicotine-induced N2-neutrophils in the progression of brain metastasis. We also demonstrated that inhibiting nicotine-induced STAT3-mediated neutrophil polarization effectively abrogated brain metastasis in vivo. Our results revealed a novel mechanistic insight on how chronic nicotine exposure contributes to worse clinical outcome of metastatic lung cancer and implicated the risk of using nicotine gateway for smoking cessation in cancer patients.
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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.