谷氨酸与HSC70结合,转导抑制IFN-β介导免疫细胞死亡的信号
Deyu Zhang1, Songze Song2, Jing Lin3
1Department of Cell Engineering, Beijing Institute of Biotechnology, Beijing 100850, China; Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China.
Developmental cell
|March 14, 2025
概括
谷氨酸通过HSC70和OTUD4发出信号,影响乳酸脱酶A (LDHA) 和免疫反应. 准这种途径通过增强T细胞招募来抑制癌症生长.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 谷氨酸对细胞信号传递和瘤发生至关重要,但其精确的信号转导机制仍然难以捉摸.
- 了解谷氨胺在癌症中的作用对于开发有效的治疗策略至关重要.
研究的目的:
- 为了阐明谷氨酸的细胞内信号通路.
- 研究谷氨酸在调节免疫细胞死亡 (ICD) 和癌症生长中的作用.
主要方法:
- 研究了谷氨胺与热冲击相关蛋白70 (HSC70) 的结合及其对otubain域含蛋白 (OTUD4) 活性的影响.
- 利用癌细胞系,患者衍生器官和异种移植来研究谷氨酸的耗尽和转移抑制.
- 评估了对乳酸脱酶A (LDHA) 稳定,乳酸生产和干扰素-β (IFN-β) 表达的影响.
主要成果:
- 谷氨酸与HSC70结合,独立于已知的代谢途径激活OTUD4,导致LDHA稳定和乳酸生产增加.
- 谷氨酸耗尽或运输抑制与化疗药物协同作用,增强IFN-β,促进CD8+T细胞透,并通过OTUD4/LDHA轴抑制瘤生长.
- 在癌症患者中,CD8表达与ASCT2,OTUD4和LDHA相反相关.
结论:
- 确定了一种新的细胞内谷氨酸信号通路,涉及HSC70,OTUD4和LDHA.
- 针对这种途径是癌症治疗的有希望的策略,特别是通过增强抗瘤免疫力.
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