缺乏葡萄糖有助于瘤细胞中KRAS途径突变的发展
Jihye Yun1, Carlo Rago, Ian Cheong
1Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
低葡萄糖环境可以通过驱动KRAS和BRAF基因的突变来促进癌症的生长. 这通过增加葡萄糖载体-1 (GLUT1) 表达发生,增强糖解和在营养应激下细胞存活.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 代谢途径 代谢途径
背景情况:
- 瘤进展受遗传突变和环境因素的影响.
- 环境条件在选择特定癌症突变中的作用尚不清楚.
研究的目的:
- 在结直肠癌中研究选择KRAS或BRAF突变的环境条件.
- 了解葡萄糖代谢在驱动这些特定遗传变化的作用.
主要方法:
- 对配对结直肠癌细胞系与不同的KRAS/BRAF突变状态进行比较性转录组分析.
- 在低葡萄糖条件下评估葡萄糖吸收,糖解和细胞存活率.
- 评估一种糖解抑制剂 (3-甲) 对癌细胞生长的影响.
主要成果:
- 葡萄糖载体-1 (GLUT1) 在具有KRAS或BRAF突变的细胞中被持续上调.
- 突变细胞表现出增强的葡萄糖吸收,糖解以及在低葡萄糖条件下生存,这取决于GLUT1.
- 低血糖条件诱导了具有野生类型等位基因的细胞中的KRAS突变,幸存者过度表达GLUT1.
结论:
- 葡萄糖剥夺作为一种选择性压力,可以驱动人类瘤中KRAS途径突变的获取.
- 在代谢压力下,GLUT1介导的葡萄糖代谢对癌细胞的存活和增殖至关重要.
更多相关视频
09:20Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
Published on: July 6, 2021
10:13Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
Published on: August 12, 2014
相关概念视频
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
The Ras Gene
Ras is a superfamily...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
Abnormal Proliferation
