自-溶酶体功能的转录控制驱动胰腺癌代谢
Rushika M Perera1,2,3, Svetlana Stoykova1,2, Brandon N Nicolay1,3
1Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Nature
|July 14, 2015
概括
胰腺癌细胞使用一种称为自的过程通过激活转录因子来生存. 这些因素,即MiT/TFE家族,重编程细胞代谢,以维持瘤生长必需的氨基酸水平.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 细胞应激反应对于癌细胞生存和代谢平衡至关重要.
- 胰腺管道腺癌 (PDA) 在病变发生过程中严重依赖自.
- 控制PDA中自和代谢重编程的调节机制在很大程度上是未知的.
研究的目的:
- 阐明调节电路,激活PDA中的自.
- 为了确定PDA细胞代谢是如何重新编程的.
- 研究转录因子在这些过程中的作用.
主要方法:
- 对协调溶酶体生物发生和营养物质清理的转录程序的分析.
- 在人类PDA细胞中研究转录因子MiT/TFE家族 (MITF,TFE3,TFEB).
- 全球代谢物分析,以评估代谢变化.
主要成果:
- 在PDA中诱导自是转录程序的一部分,由MiT/TFE转录因子介导.
- MiT/TFE蛋白与细胞质保留脱,导致核进口增加.
- MiT/TFE激活驱动 lysosomal 代谢功能,对于维持 PDA 中细胞内氨基酸池至关重要.
结论:
- MiT/TFE蛋白质是胰腺癌中代谢重编程的主调节者.
- lysosome-centric清除途径的转录激活是侵袭性胰腺癌的一个关键特征.
- 针对MiT/TFE介导的途径可以为PDA提供新的治疗策略.
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