果糖-1,6-双酸酶反对癌的进展
Bo Li1, Bo Qiu1, David S M Lee2
1Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nature
|July 22, 2014
概括
果糖-1,6-双酸酶1 (FBP1) 在清细胞细胞癌 (ccRCC) 中始终丢失. FBP1通过阻断糖解和抑制缺氧诱导因子 (HIF) 活性来抑制ccRCC的进展.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 清细胞细胞癌 (ccRCC) 表现出代谢变化,如增加的葡萄糖和脂肪,与VHL突变和HIF稳定有关.
- 以前的小鼠模型具有特异性VHL删除并没有完全复制ccRCC代谢表型,这表明了额外的贡献因素.
- 表观遗传变化,包括染色质重塑酶的丧失,都与ccRCC的发展有关.
研究的目的:
- 调查代谢变化和表观遗传变化在ccRCC病变发生中的作用.
- 为了确定在ccRCC瘤中均改变的关键分子参与者.
- 阐明FBP1抑制ccRCC进展的机制.
主要方法:
- 综合性方法结合了泛代谢分析和代谢基因组分析.
- 分析了600多个ccRCC瘤,以评估FBP1表达.
- 在管状上皮细胞和pVHL缺乏的ccRCC细胞中研究FBP1的功能机制.
主要成果:
- 果糖-1,6-双酸酶1 (FBP1) 在所有检查的ccRCC瘤中均耗尽.
- 染色体9q22上的FBP1位点丢失与ccRCC预后不佳相关.
- FBP1通过对抗糖解,并独立于其催化活性,通过抑制pVHL缺乏细胞中的核HIF功能来抑制ccRCC的进展.
结论:
- 通过双重机制,FBP1在ccRCC中起到关键的瘤抑制作用.
- FBP1的无处不在的枯竭和双重功能解释了它在ccRCC病变发生中的重要性.
- FBP1代表了一种独特的瘤抑制剂,与ccRCC中不一致的突变不同.
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