在肝细胞癌中,FGF21通过mTOR-HIF1α轴影响糖解过程
Walizeb Khan1, Ahmad Zeb1, Muhammad Faraz Arshad Malik1
1Department of Biosciences, COMSATS University, Islamabad 45550, Pakistan.
Cellular signalling
|November 23, 2024
概括
纤维细胞生长因子21 (FGF21) 通过mTOR-HIF1α轴调节肝细胞癌 (HCC) 中的葡萄糖代谢. FGF21影响糖解,影响HCC中的细胞增殖和代谢适应.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 代谢重编程,特别是糖分解,在癌症和免疫反应中至关重要.
- 纤维细胞生长因子21 (FGF21) 在肝细胞葡萄糖代谢中的作用已知,但它对有氧糖解和肝细胞癌 (HCC) 细胞生长的具体影响需要进一步调查.
- 这项研究探讨了FGF21调节HCC中的葡萄糖代谢,通过哺乳动物的目标拉巴胺素 (mTOR) 和缺氧诱导因子1-alpha (HIF1α) 轴.
研究的目的:
- 研究FGF21在HCC中调节葡萄糖代谢中的作用.
- 阐明mTOR和HIF1α信号通路在FGF21对HCC的影响中的参与.
- 为了确定FGF21失调在HCC的预后意义.
主要方法:
- 使用StringDB进行化分析,以确定FGF21和与糖解相关的基因之间的相互作用.
- 在HepG2细胞系中进行体外验证,涉及FGF21转染/沉默.
- 通过RT-PCR评估糖解标记物 (葡萄糖吸收,乳酸盐,糖解酶) 和信号通路组件 (mTOR,HIF1α).
主要成果:
- 在分析中,FGF21-mTOR-HIF1α轴被确定为葡萄糖代谢的关键调节器,mTOR作为中央集成器.
- 在HepG2细胞中抑制FGF21降低了糖解,葡萄糖吸收,乳酸生产和细胞增殖.
- 相反,复合FGF21治疗逆转了这些效应,调节了mTOR和HIF1α的表达,证实了FGF21通过这个轴在代谢调节中的作用.
结论:
- 通过mTOR-HIF1α信号通路,FGF21显著影响HCC中的糖解.
- 这一规则对于对能量可用性的代谢适应至关重要,并影响HCC的进展.
- FGF21成为HCC代谢重编程的关键参与者.
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