TAB182通过控制LDHA转录来调节糖分代谢,以影响瘤的放射敏感性
Shi Chen1,2, Da-Fei Xie2, Saiyu Li2,3
1School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan Province, 421001, P. R. China.
Cell death & disease
|March 14, 2024
概括
研究人员发现,TAB182蛋白通过增加糖解和乳酸生产,促进癌细胞的抗辐射能力. 抑制TAB182增强了辐射敏感性,为改善放射治疗结果提供了潜在的策略.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 辐射生物学 辐射生物学
背景情况:
- 代谢重编程是癌症的一个关键特征,影响瘤的生长和进展.
- 糖溶解的改变对癌细胞的辐射耐药性至关重要,但潜在的机制仍然不清楚.
研究的目的:
- 研究TAB182在对电离辐射的反应中调节糖解和乳酸生产中的作用.
- 为了确定是否针对TAB182可以克服瘤的放射电阻.
主要方法:
- 对癌细胞进行辐射,并测量TAB182蛋白水平.
- TAB182 敲除实验和对代谢变化 (乳酸盐,酸盐,ATP) 的分析.
- 研究TAB182对LDHA转录因子 (SP1,c-MYC) 的作用以及使用小鼠异种移植模型的体内研究.
主要成果:
- 照射显著增加了TAB182蛋白质的产生.
- 淘汰TAB182降低了乳酸生产,增加了酸盐和ATP水平,并逆转了辐射诱导的代谢变化.
- TAB182对于通过SP1和c-MYC的辐射诱导的LDHA转录激活至关重要.
- 准TAB182可以在体内提高瘤的辐射敏感性.
结论:
- 在对电离辐射的反应中,TAB182在调节癌细胞糖解和乳酸盐产生方面发挥着至关重要的作用.
- 抑制TAB182通过抑制代谢适应,使瘤对放射治疗重新敏感.
- 向TAB182代表了克服瘤放射电阻的有希望的策略.
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