截断的APC通过准结直肠癌中线粒体上的MAVS来破坏先天免疫反应
Si-Yu Li1,2, Xin-Yi Wang1, Jing Wang3
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, 510060, P. R. China.
Journal of translational medicine
|November 11, 2025
概括
截断的腺多样性大肠杆菌 (APC) 蛋白质抑制了结直肠癌 (CRC) 的瘤免疫力. 移除Trunc-APC并使用表观遗传疗法可以增强抗瘤反应并抑制CRC生长.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 突变腺瘤性多样性大肠杆菌 (APC) 基因产生截断APC (Trunc-APC),作为结直肠癌 (CRC) 的瘤基因.
- 在调节瘤细胞天生的免疫反应中Trunc-APC的作用基本上是未知的.
研究的目的:
- 研究Trunc-APC在CRC中的免疫调节功能.
- 确定Trunc-APC如何影响天生的免疫力及其作为治疗点的潜力.
主要方法:
- 在CRC细胞系中,CRISPR-Cas9基因编辑以淘汰突变APC.
- 转录组测序,亚细胞分离和蛋白质相互作用研究.
- 在体外和体内评估Trunc-APC缺失对免疫激活,亡和瘤生长的影响,单独和与表观遗传剂一起.
主要成果:
- Trunc-APC定位在线粒体外膜上,结合MAVS抑制I型干扰素信号传递并破坏RIG-I相互作用.
- Trunc-APC删除增强了先天性免疫激活和瘤细胞亡.
- 结合Trunc-APC删除与表观遗传疗法 (5-azacytidine和trichostatin A) 显著抑制了CRC瘤的生长.
结论:
- 在CRC中,Trunc-APC在抑制瘤内在的先天免疫力方面发挥着新的作用.
- 与表观遗传疗法共同准Trunc-APC是一种有希望的策略,可以增强CRC的抗瘤免疫力.
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