通过RBM39重新编程肝癌中的代谢
Dirk Mossmann1, Christoph Müller1, Sujin Park1
1Biozentrum, University of Basel, 4056 Basel, Switzerland.
Cell
|October 7, 2023
概括
在肝细胞癌 (HCC) 中,高氨酸水平通过重编程细胞代谢促进瘤生长. 通过增加氨酸吸收和涉及RNA结合动机蛋白39 (RBM39) 的反循环发生这种情况.
科学领域:
- 癌症学
- 代谢途径
- 癌症生物学
背景情况:
- 代谢重编程是癌症的一个关键特征,但其潜在机制及其在瘤发生性中的作用尚未完全理解.
- 细胞代谢的改变对癌症的发展和进展有显著的影响.
研究的目的:
- 研究素代谢在肝细胞癌 (HCC) 发展中的作用.
- 阐明改变氨酸水平促进瘤发生的机制.
主要方法:
- 在小鼠和患者的HCC样本中分析氨酸水平.
- 研究素的吸收和转化途径.
- 对阿尔金因对全球代谢重编程的影响的评估.
- 分子标的鉴定,包括参与阿基因介导的代谢控制的RNA结合基因蛋白39 (RBM39).
主要成果:
- 由于吸收增加和转化为多氨酸的减少,尽管合成减少,但HCC中的氨酸水平较高.
- 在葡萄糖,氨基酸,核酸和脂肪酸路径中驱动代谢重编程.
- 氨酸与RBM39结合,调节代谢基因表达.
- 增加阿斯巴拉金的合成,增强阿尔金因的吸收并创建一个积极的反循环.
结论:
- 氨酸在HCC中起到关键的信号分子作用,重编程细胞代谢以促进瘤生长.
- 氨酸-RBM39-氨酸轴是维持HCC瘤代谢的新机制.
- 针对阿尔金因代谢可以为HCC提供新的治疗策略.
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