转录因子EB (TFEB) 的活性增加了TNBC干细胞对代谢应激的抵抗力
Milad Soleimani1,2, Mark Duchow2, Ria Goyal2
1Interdisciplinary Life Sciences Graduate Programs, The University of Texas at Austin, Austin, TX, USA.
Life science alliance
|January 15, 2025
概括
转录因子EB (TFEB) 调节乳腺癌干细胞 (CSC) 的新陈代谢. TFEB对中央集团有影响
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 乳腺癌干细胞 (CSCs) 驱动瘤异质性和治疗耐药性,特别是在三阴性乳腺癌中.
- 针对CSC是具有挑战性的,因为它们的代谢适应性和缺乏定义的监管机制.
- 转录因子EB (TFEB) 与细胞代谢有关.
研究的目的:
- 研究TFEB在调节CSC新陈代谢和对代谢压力的反应中的作用.
- 阐明TFEB影响CSC特性和生存的机制.
主要方法:
- 在CSC中进行TFEB敲击 (KD).
- 在体外的乳腺球形成测定和体内瘤启动研究.
- 对CSC标记物 (CD44高/CD24低),TFEB核转位,展开蛋白质反应 (UPR) 媒介物 (BiP/HSPA5,CHOP) 和自的分析.
主要成果:
- TFEB KD抑制了CSC自我更新,乳球形成和瘤生长.
- TFEB KD减少了CD44高/CD24低细胞的比例.
- 2-脱氧-D-葡萄糖 (2-DG) 治疗诱导了TFEB核转位和UPR,该转位和UPR被TFEB KD削弱.
- TFEB KD减弱了2DG诱导的自,这表明TFEB在代谢压力下促进CSC存活.
结论:
- TFEB在调节三阴性乳腺癌中CSCs的代谢应激反应方面发挥着至关重要的作用.
- TFEB通过涉及自和展开蛋白质反应 (UPR) 的机制调节CSC.
- 在三阴性乳腺癌中,TFEB代表了克服治疗耐药性的潜在治疗标.
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