由USP8控制的GPX4恒温调节铁和癌症免疫疗法
Haiou Li1, Yishuang Sun1,2, Yingmeng Yao1,2
1Department of Dermatology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
概括
针对ferroptosis的调节者USP8,可以增强癌症免疫疗法. 抑制USP8会破坏GPX4的稳定性,使癌细胞对ferroptosis敏感,并促进抗PD-1反应.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 铁,一种依赖于铁的细胞死亡,对健康和疾病至关重要,但其调节机制尚未完全理解.
- 了解铁亡调节是开发癌症等疾病新疗法策略的关键.
研究的目的:
- 为了研究在ferroptosis调节中的ubiquitin特定蛋白酶8 (USP8) 的作用.
- 探索针对USP8进行癌症治疗和免疫治疗的潜力.
主要方法:
- 使用小鼠模型在肠上皮细胞 (IECs) 中有针对性的USP8删除.
- 研究USP8与谷氨过氧化酶4 (GPX4) 的相互作用和调节.
- 评估USP8抑制对癌细胞铁灭敏感性和瘤生长 in vitro 和 in vivo 的影响.
主要成果:
- 在IEC中 homozygous Usp8 删除导致结肠上皮的变化,并缩短了寿命.
- 异卵性Usp8删除赋予了对结直肠瘤发生的抗性.
- USP8稳定了GPX4;它的抑制使癌细胞对铁亡敏感.
- 结合铁灭诱导剂的USP8抑制降低了瘤生长和增加了CD8+ T细胞透,增强了抗PD-1免疫疗法反应.
结论:
- USP8通过稳定GPX4.4来对抗铁.
- 针对USP8是一个有前途的策略,以增强基于ferroptosis的癌症疗法和免疫治疗.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K