DFFB抑制干扰素,使癌细胞持续生长
bioRxiv : the preprint server for biology
|September 2, 2025
概括
在向治疗中生存的癌细胞会被干扰素信号阻断成长. 矛盾的是,这些细胞使用细胞灭绝来抑制这种信号,
科学领域:
- 分子生物学
- 癌症研究
- 免疫学
背景情况:
- 有针对性的癌症疗法可能会引起深度反应, 但往往会导致药物耐药性.
- 瘤进化和多种抗药机制使抗药性癌症的治疗复杂化.
- 了解和预防适应性抵抗机制对于有效的癌症治疗至关重要.
研究的目的:
- 研究残留癌细胞在瘤基因向治疗中存活的机制.
- 确定癌症持续细胞中启动耐药性的适应过程.
- 确定持续细胞如何逃脱生长停止并促进瘤的再生.
主要方法:
- 对瘤基因向治疗中存活的残留癌细胞的分析.
- 研究了I型干扰素 (IFN) 信号在生长停止中的作用.
- 检查了亡机器,DNA碎片化因子B (DFFB/CAD) 和激活转录因子3 (ATF3) 在持续细胞适应中的参与.
主要成果:
- 药物压力会诱导内在的I型干扰素 (IFN) 信号,导致癌症细胞的生长停止.
- 持久性细胞通过利用亡途径来抑制干扰素刺激的基因 (ISG).
- 卡斯帕酶对DFFB/ CAD的潜致激活导致ISG的ATF3中介抑制,从而促进细胞的持续再生.
- 缺乏DFFB或ATF3的持续细胞表现出高ISG表达,并且无法再生.
结论:
- 矛盾的是, 死亡前的亡应激会促使剩余的癌细胞在药物治疗中生存.
- DFFB-ATF3轴对于癌症持续细胞来说至关重要,以克服IFN诱导的生长停止并获得耐药性.
- 针对这种由亡驱动的适应机制可以为克服癌症治疗中所获得的抗药性提供新的策略.
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