针对YAP活动和谷氨胺代谢,通过防止细胞外基质积累,共同抑制瘤进展
Mihyang Park1,2, Jonghwa Jin1, Da Young An3
1Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
Cancer research
|July 29, 2024
概括
向癌细胞的谷氨酸代谢激活了YAP信号,增加了细胞外基质沉积. 将YAP抑制剂与谷氨胺代谢抑制剂结合起来,有效抑制瘤生长并减少矩阵积累.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 分子生物学分子生物学
背景情况:
- 癌细胞通过各种机制对谷氨酸代谢抑制剂产生抵抗力.
- 瘤对改变的谷氨胺可用性的反应为组合策略提供了潜在的治疗点.
研究的目的:
- 研究向谷氨胺利用影响癌细胞信号传递和瘤微环境的机制.
- 确定增强谷氨酸代谢抑制剂疗效的策略.
主要方法:
- 研究了抑制谷氨胺利用对YES相关蛋白 (YAP) 信号传递的影响.
- 评估了YAP激活在细胞外基质 (ECM) 沉积中的作用.
- 在体内评估了YAP和谷氨胺利用抑制的协同效应.
- 研究了阻断ECM重塑对治疗疗效的影响.
主要成果:
- 抑制谷氨胺利用通过减少LATS酸化刺激了YAP信号传递.
- 激活的YAP通过结缔组织生长因子分泌增加了ECM沉积,促进了纤维细胞的纤维菌素和原生成.
- 联合抑制YAP和谷氨胺利用在体内协同抑制瘤生长,降低ECM沉积.
- 阻止ECM重塑增强了谷氨胺利用抑制剂的瘤抑制作用.
结论:
- 向谷氨胺利用激活YAP,导致纤维细胞增加ECM沉积.
- YAP抑制剂和抗纤维素策略代表了癌症组合代谢疗法的有希望的方法.
- 降低ECM水平可以提高谷氨胺代谢抑制剂的疗效.
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