癌细胞存活率中的cyclin D3-CDK6激酶的代谢功能
Haizhen Wang1,2, Brandon N Nicolay3, Joel M Chick4
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Nature
|June 14, 2017
概括
循环D3-CDK6激酶通过重定向糖解来调节癌细胞代谢. 抑制这种复合物会耗尽抗氧化剂,增加反应性氧物种并导致癌细胞死亡.
科学领域:
- 癌症学
- 分子生物学
- 癌症新陈代谢
背景情况:
- D型循环素和循环素依赖性激酶 (CDKs) 4/6对于细胞增殖至关重要.
- 在临床癌症试验中,CDK4/ 6抑制剂显示出有前途.
研究的目的:
- 研究D3-CDK6在癌细胞代谢中的作用及其治疗影响.
主要方法:
- 在小鼠中利用人类癌细胞和患者衍生的异种移植.
- 分析了cyclin D3-CDK6对糖解酶和代谢途径的影响.
主要成果:
- 素D3-CDK6可化并抑制6 - 果酸酶和酸盐激酶M2.
- 这将中间体重定向到酸盐 (PPP) 和血清路径.
- 抑制D3-CDK6会消耗NADPH和谷氨,从而增加反应性氧物种并诱导亡.
结论:
- 循环D3-CDK6与细胞循环和新陈代谢联系在一起,作为瘤蛋白.
- 测量cyclin D3-CDK6水平可以发现对CDK4/6抑制治疗有反应的瘤.
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