Sleep deprivation-induced sympathetic activation promotes pro-tumoral macrophage phenotype via the ADRB2/KLF4 pathway to facilitate NSCLC metastasis

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-03-30 DOI:10.1016/j.isci.2025.112321

Shuxian Yin , Jiali Wang , Yunlong Jia , Xiaoyi Wang , Yan Zhao , Tianxu Liu , Wei Lv , Yuqing Duan , Song Zhao , Sheng Wang , Lihua Liu

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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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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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