乳酸激活GPR81会导致瘤诱导的缓解症
Xidan Liu1, Shijin Li1, Qionghua Cui1
1Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Nature metabolism
|March 19, 2024
概括
升高的乳酸水平通过激活脂肪组织中的G蛋白结合受体81 (GPR81) 来驱动癌症缓解症. 准GPR81可能为这种严重的癌症并发症提供一种新的治疗方法.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 代谢过程中的代谢.
背景情况:
- 卷发症影响50-80%的癌症患者,导致20%的癌症死亡.
- 驱动癌症缓解症的精确机制尚未完全理解.
研究的目的:
- 调查乳酸和G蛋白结合受体81 (GPR81) 在癌症缓解症中的作用.
- 阐明乳酸诱导性缓解症中涉及的信号通路.
主要方法:
- 在癌症患者和小鼠模型中,循环乳酸水平和体重减轻的相关分析.
- 在没有瘤的小鼠中进行乳酸注试验.
- 涉及脂肪特异性和全球GPR81缺乏的小鼠的研究.
- 研究乳酸/GPR81激活下游的信号级联.
主要成果:
- 循环中的乳酸水平与癌症缓解症的体重减轻具有积极的相关性.
- 单独注入乳酸盐可以在小鼠中诱导一种可塞性表型.
- 脂肪组织中GPR81的缺乏改善了卡赫克西亚,将其确定为一个关键的调解者.
- 乳酸酸/GPR81诱导的缓解症涉及一个Gi-Gβγ-RhoA/ROCK1-p38信号通路,独立于蛋白激酶A.
结论:
- 乳酸是癌症缓解症的一个关键驱动因素.
- 脂肪GPR81是乳酸的催化作用的关键调解者.
- 向乳酸/GPR81通路为癌症缓存症提供了潜在的治疗策略.
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