细胞外基质重塑通过TXNIP破坏稳定性调节葡萄糖代谢
William J Sullivan1, Peter J Mullen2, Ernst W Schmid2
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Cell
|September 11, 2018
概括
细胞外基质重塑调节细胞代谢. 通过降解TXNIP,增强细胞表面的葡萄糖转运体GLUT1,促进细胞迁移,从而增加了氨酸酶治疗.
科学领域:
- 细胞生物学
- 生物化学
- 癌症研究
背景情况:
- 细胞代谢受到外部因素的影响,如营养素和生长信号.
- 细胞外基质 (ECM) 改造被认为是细胞外部代谢控制的关键调节者.
研究的目的:
- 研究ECM重塑在细胞代谢调节中的作用.
- 确定将ECM组件与代谢途径联系起来的特定分子机制.
主要方法:
- 对癌细胞中的糖解驱动因素进行无偏见的分析.
- 用氨酸酶治疗细胞和异种移植.
- 对受体激素激酶信号和mRNA衰变因子的分析.
- 评估葡萄糖输送器GLUT1的定位和功能.
- 细胞迁移试验的评估.
主要成果:
- 氨酸介导的运动受体与癌症中的糖分分解有很强的相关性.
- 氨酸酶治疗显著增加糖分分解.
- 这种增加是由ZFP36诱导,针对TXNIP进行降解.
- 降低TXNIP会导致血膜GLUT1的增加,从而增加葡萄糖的吸收.
- 氨酶诱导的糖解对于加速细胞迁移至关重要.
结论:
- 通过调节糖解,ECM重塑,特别是氨酸降解,直接影响细胞代谢.
- 涉及氨酸介导运动受体,ZFP36,TXNIP和GLUT1的已确定途径提供了将ECM与代谢联系起来的新机制.
- 这种ECM的代谢调节对于动态生物过程如瘤生成和胚胎生成至关重要.
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