由UPR诱导的细胞内C5aR1促进适应低毒瘤微环境
Tatsuya Suwa1, Kelly Sw Lee1, Ian J Chai1
1Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, United Kingdom.
Cell death & disease
|July 22, 2025
概括
瘤微环境条件如低氧会增加C5a受体1 (C5aR1) 的表达和细胞内定位. 这种C5aR1信号传递有助于瘤细胞的生存和适应,建议新的癌症治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
背景情况:
- C5a-C5a受体1 (C5aR1) 轴与炎症和免疫病理有关.
- 虽然细胞膜表达已知,但细胞内C5aR1在炎症功能中的作用正在出现.
- 控制C5aR1表达和局部化的机制,特别是在瘤中,尚不清楚.
研究的目的:
- 研究瘤微环境条件如何调节C5aR1的表达和定位.
- 阐明细胞内C5aR1在瘤细胞适应缺氧中的作用.
- 探索针对癌症中C5a/C5aR1轴的治疗策略.
主要方法:
- 在瘤微环境的不同物理条件下研究C5aR1表达和局部化.
- 利用遗传学和药理学的方法来准C5a/C5aR1轴.
- 在低氧条件下评估C5aR1对细胞过程如自和亡的影响.
主要成果:
- 低氧诱导C5aR1表达通过展开的蛋白质反应 (UPR) 和内质网膜 (ER) 压力.
- 缺氧促进C5aR1内细胞分裂,导致其细胞内积累.
- C5aR1通过调节自和亡来调节瘤细胞适应缺氧.
- 具有高度细胞透性的C5aR1抑制剂对细胞存活有显著影响.
结论:
- 低氧诱导的C5aR1表达和细胞内局部化在免疫抑制微环境中促进瘤细胞的存活.
- 针对C5a/C5aR1轴,特别是通过透性抑制剂,为癌症提供了潜在的治疗策略.
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