一个GSTP1介导的乳酸信号通过PPP氧化分支促进瘤发生
Yandi Sun1,2, Qian He3,4, Jingjia Li3,4
1Cancer Institute, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Cell death & disease
|July 25, 2023
概括
乳酸通过GSTP1传感器激活葡萄糖代谢,促进癌细胞生存,增强对氧化应激的抵抗力. 准这种途径可能会减少瘤生长并改善乳腺癌治疗.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 乳酸酸化在固体瘤中很常见,有助于癌细胞适应代谢应激.
- 乳酸影响癌细胞氧化还原平衡的精确机制尚未完全理解.
研究的目的:
- 阐明乳酸在癌细胞氧化还原平衡中的作用.
- 研究乳酸对G6PD调节的机制及其对瘤生长的影响.
主要方法:
- 研究了GSTP1-G6PD-SRC复合体的形成.
- 评估了乳酸对G6PD活性和酸化的影响.
- 利用乳腺癌细胞模型研究废除GSTP1介导信号的影响.
- 在患者瘤样本中,相关的SRC蛋白水平和G6PD酸化.
主要成果:
- 乳酸通过与GSTP1结合来减弱SRC介导的G6PD酸化.
- 乳酸通过GSTP1增强G6PD活性和酸通路 (PPP),促进NADPH生产和反应性氧物种 (ROS) 耐药性.
- 干扰GSTP1-乳酸盐信号传递减少了乳腺癌细胞中的瘤生长和ROS抗性.
- 在特定乳腺癌亚型 (ER/PR阳性或HER2阴性) 中观察到SRC和G6PD化之间的正相关性.
结论:
- GSTP1作为一种新的乳酸盐传感器,调解癌细胞适应代谢压力的过程.
- 依赖GSTP1的乳酸信号对瘤发育和抗氧化应激的抵抗至关重要.
- 针对GSTP1-乳酸盐-G6PD轴为乳腺癌提供了一个潜在的治疗策略.
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