乳酸诱导瘤通过LAR因子依赖的阴阳1降解的进展
Shujuan Du1, Xiaoting Chen1, Xiao Han2
1MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganism and Infection, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, P. R. China.
高血乳酸通过减少阴阳1 (YY1) 表达来促进癌症. 乳酸酸通过特定的动机触发YY1降解,低YY1水平提高瘤的生长和扩散.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 代谢重编程,特别是有氧糖解,是癌症的标志.
- 血乳酸水平升高与各种人类恶性瘤有关,但分子机制尚不清楚.
研究的目的:
- 阐明乳酸影响癌症进展的分子机制.
- 确定阴阳1 (YY1) 在乳酸媒介癌症发展中的作用.
主要方法:
- 研究了癌细胞系 (B淋巴瘤,宫癌) 中的乳酸盐水平和YY1表达之间的相关性.
- 利用基于细胞的测试和小鼠异种移植模型来研究YY1降解及其对癌症表型的影响.
- 检查了在YY1调节中胺丰富的乳酸反应 (LAR) 基因的作用.
主要成果:
- 在乳糖含量高的癌症中观察到YY1表达的减少.
- 乳酸诱导YY1核出口和通过HSP70介导的自通过LAR动机通过YY1核出口和降解.
- 突变LAR动机可以防止YY1的降解,并促进亡.
- 低YY1表达增强癌细胞的增殖,入侵,血管生成和瘤生长 in vivo.
结论:
- 乳酸盐通过其LAR动机诱导YY1降解来促进癌症的进展.
- 在高乳酸盐的环境中,YY1起到瘤抑制作用.
- LAR动机和YY1代表了癌症治疗的潜在治疗点.
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