口腔链球菌 Salivarius 情侣 中性细胞 IRGM1 信号到 NET 形成和结肠直肠癌转移
Fengyi Liu1,2, Yuan Wang3, Hengxuan Cai2
1Department of Integrated Traditional Chinese and Western Medicine, First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 28, 2026
概括
口腔细菌Streptococcus salivarius通过涉及IRGM1和IQGAP1的特定分子途径触发中性粒细胞外细胞陷 (NET) 形成,驱动结肠直肠癌 (CRC) 转移.
科学领域:
- 微生物学 微生物学
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 口腔微生物群可以转移到胃肠道,影响肠道免疫力.
- 连接口腔细菌与远端器官转移的机制,特别是在结直肠癌 (CRC) 中,尚未完全理解.
研究的目的:
- 阐明口腔微生物群,特别是Streptococcus salivarius在促进CRC转移中的作用.
- 为了确定参与口腔微生物群诱导的转移的分子途径.
主要方法:
- 研究了Streptococcus salivarius对中性粒细胞外细胞陷 (NET) 形成的影响.
- 使用分子技术来识别蛋白质相互作用和信号通路 (IRGM1-IQGAP1,Wnt5a,PI3K/AKT).
- 使用基因操纵 (IRGM1的条件删除) 和药理抑制 (XAV-939) 进行功能验证.
- 分析了CRC患者的临床样本,以评估S. salivarius的丰度.
主要成果:
- 发现Streptococcus salivarius通过诱导NET形成来促进CRC转移.
- 一个关键的机制涉及IRGM1-IQGAP1复合物的形成,激活Wnt5a信号和PI3K/AKT通路,导致NETosis.
- 条件删除IRGM1或抑制下游信号传输显著减少了S. salivarius诱导的NET形成.
- 在CRC患者的口腔,便和瘤微环境样本中丰富了S. salivarius.
结论:
- 确定了一种新的机制,即Streptococcus salivarius通过IRGM1-IQGAP1-介导的Wnt5a-PI3K/AKT信号传递驱动CRC转移,从而导致NET的形成.
- 这一途径代表了口腔微生物群和中性粒细胞驱动的免疫反应在癌症进展中的关键联系.
- 这些发现凸显了向这种途径对抗CRC转移的潜力.
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