ArticleiScience2025
Sleep deprivation-induced sympathetic activation promotes pro-tumoral macrophage phenotype via the ADRB2/KLF4 pathway to facilitate NSCLC metastasis.
Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- Si Ni Powder enhances chemotherapy efficacy in sleep-deprived breast cancer via modulation of the tumor microenvironment.Translational cancer research · 2026Article
- Article
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- Brain-cancer interactions outside the CNS.Oncogene · 2026Review
- Review
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Authors and funding
11 authors.
Funding
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Abstract
Sleep deprivation is one of concomitant symptoms of cancer patients, particularly those with non-small cell lung cancer (NSCLC). The potential effect of sleep deprivation on tumor progression and underlying mechanisms remain to be fully investigated. Using a sleep-deprived tumor-bearing mouse model, we found that sleep deprivation altered immune cell composition and regulated pro-tumoral M2 macrophage polarization by the sympathetic nervous system. Furthermore, we identified a role of catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) in influencing NSCLC metastasis. Clinical analyses revealed a correlation between sympathetic-related indicators and poor prognosis. Mechanistically, our findings indicate that sleep deprivation facilitates the polarization of pro-tumoral macrophages by upregulating β2-adrenergic receptor (ADRB2), which subsequently enhances the expression of Kruppel-like transcription factor 4 (KLF4) through the JAK1/STAT6 phosphorylation pathway. These findings highlight a neuro-immune mechanism linking sleep deprivation to NSCLC metastasis, suggesting that targeting the ADRB2/KLF4 axis could improve outcomes for sleep-deprived NSCLC patients.
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Registered trials
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