由关键代谢物枯竭引起的表观遗传重编程是一种进化古老的瘤发生途径
Zhe Chen1, Xiaomeng Zhang1, Mingxi Deng1
1Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China.
Disease models & mechanisms
|June 16, 2025
概括
瘤生成可以通过代谢变化,而不是仅仅是突变,在短命物种中迅速发生. 削减关键代谢物,如乙-CoA和S-adenosyl metionin驱动跨物种的瘤生长,这表明癌症发展的古代起源.
科学领域:
- 进化生物学是进化的生物学.
- 癌症研究 癌症研究
- 代谢学 代谢学 代谢学
背景情况:
- 瘤发生通常需要数年时间和人类的多个突变.
- 短寿命物种中的瘤可以迅速形成,质疑常见的途径.
- 了解瘤发生的保存机制至关重要.
研究的目的:
- 为了研究跨物种瘤发生途径的共同点.
- 在模型中确定驱动瘤形成的关键代谢变化.
- 探索癌症发展的进化起源.
主要方法:
- 利用Drosophila melanogaster瘤模型诱导的细胞极性基因的损失.
- 分析了系统代谢变化,包括乙-CoA和氨酸循环.
- 在和人类瘤中进行了具有相似代谢特征的比较研究.
主要成果:
- 鉴定了乙-CoA的全身性耗尽,减少了基因素乙化和基因沉默.
- 观察到氨酸循环中的缺陷,耗尽S-adenosyl氨酸,降低基因素甲基化,并激活转子子体.
- 证明扰乱 metionin 代谢会抑制瘤的生长.
- 发现具有相似代谢概况的人类瘤表现出较低的突变负载,较年轻的患者年龄和减少的DNA甲基化.
结论:
- 代谢变化,特别是关键代谢物的耗尽,是瘤发生的进化古老驱动因素.
- 这种代谢重编程可以导致迅速的瘤形成,而不依赖于广泛的突变.
- 研究结果表明,物种之间保存的代谢脆弱性有助于癌症的发展.
关键词:
这种植物是Drosophila melanogaster.乙-甲酸是一种表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.无脊椎动物的瘤模型代谢过程中的代谢.这是一种S-Adenosyl metionin.更多相关视频
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