无感受神经元保护癌细胞免受氧化应激
Yu Zhang1, Mingtao Chen2, Xiaohu Lin3
1Department of Oral and Maxillofacial Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cell reports
|March 14, 2026
概括
无感受神经元通过增加Lnc-GCLC-1表达来帮助头癌细胞在氧化压力下生存,这会激活NRF2通路. 准这种途径可能会提高癌症治疗的疗效.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 神经科学是一个神经科学.
背景情况:
- 瘤微环境 (TME) 在癌症进展中起着至关重要的作用.
- 癌细胞在TME中管理氧化应激的机制尚未完全理解.
- 头部和部状细胞癌 (HNSCC) 的生存策略需要进一步阐明.
研究的目的:
- 研究 nociceptive神经元在HNSCC细胞存活中的作用.
- 确定参与HNSCC.氧化应激抵抗的分子途径.
- 探索神经元与癌细胞相互作用中的潜在治疗点.
主要方法:
- 研究了感知神经元和HNSCC细胞之间的相互作用.
- 分析了Lnc-GCLC-1,epiregulin (EREG),Ets变体4 (ETV4),Kelch样ECH相关蛋白1 (KEAP1) 和NRF2信号的表达和功能.
- 利用细胞培养模型和分析患者数据进行HNSCC预后.
主要成果:
- 无感受神经元分泌epiregulin,在氧化应激下调节ETV4介导的HNSCC细胞中的Lnc-GCLC-1表达.
- 增加的Lnc-GCLC-1会破坏KEAP1-NRF2复合体,激活NRF2通路并增强谷氨 (GSH) 合成.
- 这一途径赋予了对西斯胺诱导的氧化应激的抵抗力,高的Lnc-GCLC-1与HNSCC预后不佳相关.
结论:
- 无感受神经元通过通过EREG-Lnc-GCLC-1-NRF2轴增强氧化应激抵抗来促进HNSCC的生存.
- 针对感知神经元或这个特定的分子轴提供了一个潜在的策略,以改善HNSCC治疗结果.
- 在HNSCC中,Lnc-GCLC-1是潜在的预后生物标志物.
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