INSR/AKT1轴在急性髓性白血病中促进细胞的增殖和迁移
Liman Lin1, Chunle Zhao2, Xiaoya Cai3
1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biochimica et biophysica acta. Molecular basis of disease
|December 15, 2025
概括
胰岛素受体 (INSR) 促进急性髓性白血病 (AML) 细胞的增殖和迁移. 兴奋性INSR通过激活AKT1来增强AML细胞生长和入侵,为化疗耐药性提供潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 化疗耐药性是治疗复发性和耐火性急性髓性白血病 (AML) 的重要障碍.
- 了解驱动AML化学疗法耐药性的分子机制对于开发有效治疗是至关重要的.
研究的目的:
- 研究胰岛素受体 (INSR) 在急性髓性白血病 (AML) 中的化疗耐药性中的作用.
- 阐明INSR影响AML细胞行为和增殖的分子途径.
主要方法:
- 在用奇达米德治疗的AML细胞和AML患者样本中分析INSR的基因表达.
- 过度表达和淘汰实验,以评估INSR对细胞循环,增殖,入侵和迁移的影响.
- 转录组测序和基因表达特征的交互分析,以确定相关的信号通路,重点关注AKT1.1.
主要成果:
- 在chidamide治疗后的AML细胞和AML患者中,INSR表达升高.
- 通过对维丁和N-cadherin进行上调调节,INSR过度表达促进AML细胞周期过渡 (G1到S阶段),增殖,入侵和迁移.
- AKT1表达与INSR正相关,与AML患者预后负相关.
- 抑制AKT1可以减少AML细胞的增殖和迁移,并减少INSR的增殖和迁移效应.
结论:
- 在促进AML细胞增殖和迁移方面,INSR起着至关重要的作用.
- 通过INSR介导的AML细胞生长和转移的促进取决于AKT1.1的上调.
- 准INSR/AKT1通路是一个潜在的治疗策略,可以克服AML的化疗耐药性.
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