质子感应GPCRs是沃伯格癌症遗产的缺失环节吗?
Jessica Cornell1, Samantha Rea1, Leif R Neitzel2,3
1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
概括
质子感应G蛋白合受体 (GPCRs) 可能解释Warburg效应在癌症中的持久性. 这些受体将瘤酸度与癌症生长和治疗耐药性联系起来,提供新的治疗点.
科学领域:
- 癌症生物学 癌症生物学
- 代谢重编程 代谢重编程
- 分子信号传输的方法
背景情况:
- 华堡效应,即增强的糖解产生乳酸,即使有氧,也是癌症的标志,但尽管ATP生产效率低下,但其持续性尚不清楚.
- 由于乳酸积累而产生的酸性瘤微环境促进了癌症的进展,治疗耐药性和免疫逃避.
研究的目的:
- 提出质子感应G蛋白合受体 (GPCRs) 作为将华堡效应与瘤信号联系起来的媒介.
- 阐明细胞外酸性激活GPCRs并驱动癌症表型的机制.
主要方法:
- 审查关于华堡效应,瘤微环境和GPCR信号传递的现有文献.
- 假设质子感应GPCRs,如GPR68,在转导酸性信号中的作用.
主要成果:
- 像GPR68这样的GPCR中关键残留物的质子激活下游通路 (MAPK,PI3K/Akt,Rho,β-arrestin).
- 这种激活促进癌细胞的增殖,迁移,存活和治疗耐药性.
结论:
- 质子感应GPCRs提供了沃堡效应和瘤信号传递之间的机械联系,解释了代谢悖论.
- 针对这些GPCRs可能会破坏改变癌症代谢和瘤进展之间的协同作用,提供新的治疗策略.
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