综合蛋白质组分析确定了胰腺神经内分泌瘤中依赖TYMS的AMPK-mTOR信号
Vinod Vijayakurup1, Benjamin Meyer1, Syeda Rida Rizvi1
1Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA.
iScience
|December 9, 2025
概括
在胰腺神经内分泌瘤 (PanNETs) 中基酸合成酶 (TYMS) 的过度表达通过调节AMPK-mTOR通路,通过调节AMPK-mTOR通路,将核酸代谢与癌症生长联系起来,从而影响药物耐药性和预后.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 持续胺酸合成酶 (TYMS) 过度表达是药物耐药性和晚期固体瘤 (包括胰腺神经内分泌瘤 (PanNETs)) 预后不良的生物标志物.
- TYMS对于DNA合成至关重要,但其过度表达表明其作用超出了核酸代谢.
研究的目的:
- 调查TYMS在调节癌症代谢和泛网信号通路中的作用.
- 探索TYMS,AMPK-mTOR轴和泛网治疗反应之间的联系.
主要方法:
- 蛋白质组分析以确定参与新陈代谢的TYMS调节蛋白质.
- 研究TYMS抑制和过度表达对PanNET细胞和转基因小鼠模型中的AMPK-mTOR信号通路的影响.
- 在患者获得的PanNET样本中,与mTOR相关基因对TYMS表达的相关性.
主要成果:
- TYMS调节了参与能源依赖代谢的蛋白质.
- 泰姆斯直接影响AMP激活蛋白激酶 (AMPK) - - 哺乳动物目标的拉巴胺素 (mTOR) 信号通路.
- TYMS抑制激活AMPK信号,而TYMS过度表达抑制AMPK并增强PanNET中的mTOR信号.
- TYMS表达与mTOR相关的基因具有积极的相关性,并影响PanNET患者的everolimus疗效.
结论:
- 泰姆斯在将核酸代谢与癌症生长信号通过AMPK-mTOR轴的调节进行联系方面发挥着新的作用.
- 在临床上,TYMS水平具有显著意义,影响了PanNET患者对mTOR抑制剂 (如everolimus) 的预后和反应.
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