卵巢癌细胞扩散和迁移需要FBXL18通过激活AKT信号传递来实现
Yanyan Zhuang1,2, Jiajia Xue1, Xiya Qiu3
1Center for Reproductive Medicine, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital/Medical Center of Soochow University) Suzhou 215123, Jiangsu, China.
American journal of translational research
|June 17, 2024
概括
富含F-box和氨酸的重复蛋白18 (FBXL18) 通过通过K63-链接的无化激活AKT通路来促进卵巢癌 (OC) 的生长和迁移. FBXL18可以作为OC的治疗点.
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:
- 富含F-box和氨酸的重复蛋白18 (FBXL18) 是一种E3-ubiquitin结合酶,涉及各种疾病.
- 在卵巢癌 (OC) 中FBXL18的特定作用和机制在很大程度上仍未被探索.
研究的目的:
- 研究FBXL18对卵巢癌细胞生长和瘤发生的影响.
- 阐明FBXL18在OC中的作用的基础分子机制.
主要方法:
- 在OC细胞系 (A2780,OVCAR3) 中使用siRNA和过度表达等离子体调节FBXL18表达.
- 细胞增殖,迁移和瘤发生通过CCK-8,殖民地形成,迁移试验和裸体老鼠异种移植进行了评估.
- 蛋白质相互作用和无处可见性被分析使用西方涂抹,共免疫沉和无处可见性测试,专注于FBXL18/AKT轴.
主要成果:
- FBXL18的淘汰抑制了OC细胞的增殖和迁移;过度表达具有相反的效果.
- 过度表达FBXL18增加了酸化AKT (S473) 水平,而这些水平被AKT抑制剂 (MK-2206) 逆转.
- FBXL18与AKT直接相互作用,促进K63结合的AKT无化和激活,从而增强OC细胞的增殖和迁移.
结论:
- FBXL18显著促进卵巢癌细胞的增殖,迁移和瘤发生.
- FBXL18/AKT轴,涉及FBXL18对AKT的K63结合的泛化,是OC进展的一个关键机制.
- FBXL18代表了卵巢癌的潜在诊断和治疗标.
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