通过调节IRF9/IFI6轴,TAMs衍生的外体促进乳腺癌的进展
Xingjuan Zhao1, Yajue Wang1, Xuan Yang1
1Department of Mammary Gland, Shanxi Provincial People's Hospital, Taiyuan City, 030012, Shanxi Province, China.
Breast cancer (Tokyo, Japan)
|October 2, 2025
概括
与瘤相关的巨细胞 (TAMs) 释放含有干扰素α诱导蛋白6 (IFI6) 的外体,该蛋白驱动乳腺癌 (BC) 的进展. 这通过干扰素调节因子9 (IRF9) /IFI6轴发生,突出了BC的新治疗标.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 乳腺癌 (BC) 是全球女性癌症相关死亡的主要原因.
- 瘤微环境,特别是与瘤相关的巨细胞 (TAMs) 和它们的外体,在BC进展中起着至关重要的作用.
- 通过TAM衍生的外基因组影响BC的确切机制仍然不完全理解.
研究的目的:
- 阐明TAM衍生的外体在调节乳腺癌 (BC) 进展中的作用.
- 在BC进步中调查涉及TAM衍生的外体的特定分子机制.
- 在这个过程中确定关键的分子参与者,如干扰素调节因子9 (IRF9) 和干扰素α诱导蛋白6 (IFI6).
主要方法:
- 外体从TAM中分离出来并进行了表征.
- 在体外测试 (EdU,Transwell,流细胞计) 评估了BC细胞的增殖,迁移,入侵,亡和活性氧物种 (ROS) 水平.
- 用RT-qPCR,西部抹杀,双露西法酶记者测定和染色体免疫沉 (ChIP) 来分析基因和蛋白质表达和相互作用.
- 用小鼠异种移植模型在体内验证BC瘤生长中的IRF9/IFI6轴.
主要成果:
- 发现TAMs衍生的外基因组富含干扰素α诱导蛋白6 (IFI6).
- 从TAMs传播的外体IFI6促进了BC细胞的增殖,迁移和糖解,同时抑制了细胞亡和ROS积累.
- 干扰素调节因子9 (IRF9) 被确定为TAM中IFI6转录的促进者,TAM衍生的外体内IRF9/IFI6轴被证明在体外和体内都能推动BC进展.
结论:
- 由TAM衍生的外体通过IRF9/IFI6信号轴促进乳腺癌的进展.
- 在TAM衍生的外体中准IRF9/IFI6轴为乳腺癌的潜在治疗策略.
- 了解TAM和BC细胞通过外体细胞之间的复杂通信对于开发新型癌症治疗非常重要.
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