多胺
鸟氨酸脱羧酶
细胞生物学
细胞生长
癌变
生物
河马信号通路
下调和上调
转录因子
效应器
癌症研究
化学
生物化学
基因
酶
作者
Hongde Li,Bo-Tsung Wu,Mohammed Kanchwala,Jing Cai,Li Wang,Chao Xing,Yonggang Zheng,Duojia Pan
标识
DOI:10.1038/s41556-022-00848-5
摘要
Metabolic reprogramming is central to oncogene-induced tumorigenesis by providing the necessary building blocks and energy sources, but how oncogenic signalling controls metabolites that play regulatory roles in driving cell proliferation and tumour growth is less understood. Here we show that oncogene YAP/TAZ promotes polyamine biosynthesis by activating the transcription of the rate-limiting enzyme ornithine decarboxylase 1. The increased polyamine levels, in turn, promote the hypusination of eukaryotic translation factor 5A (eIF5A) to support efficient translation of histone demethylase LSD1, a transcriptional repressor that mediates a bulk of YAP/TAZ-downregulated genes including tumour suppressors in YAP/TAZ-activated cells. Accentuating the importance of the YAP/TAZ–polyamine–eIF5A hypusination–LSD1 axis, inhibiting polyamine biosynthesis or LSD1 suppressed YAP/TAZ-induced cell proliferation and tumour growth. Given the frequent upregulation of YAP/TAZ activity and polyamine levels in diverse cancers, our identification of YAP/TAZ as an upstream regulator and LSD1 as a downstream effector of the oncometabolite polyamine offers a molecular framework in which oncogene-induced metabolic and epigenetic reprogramming coordinately drives tumorigenesis, and suggests potential therapeutic strategies in YAP/TAZ- or polyamine-dependent human malignancies. Li et al. show that YAP/TAZ directly promotes polyamine biosynthesis and activates eIF5A activity to upregulate LSD1 expression, thereby suppressing various genes including tumour suppressors to enhance tumour growth.
科研通智能强力驱动
Strongly Powered by AbleSci AI