由AXL-TBK1驱动的AKT3激活促进了转移
Emily N Arner1,2, Dina Alzhanova2, Jill M Westcott2
1Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science signaling
|December 17, 2024
概括
AXL激活触发AKT3和牛信号,促进癌症EMT和转移. 抑制AKT3可能为侵袭性癌症提供一种新疗法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症信号通路 癌症信号通路
背景情况:
- 受体氨酸激酶 (AXL) 驱动瘤进展,转移和治疗阻力.
- AXL诱导上皮层-介质细胞过渡 (EMT),这是癌症扩散的关键过程.
研究的目的:
- 阐明AXL激活的促进EMT的下游信号通路.
- 研究AKT3在AXL介导的EMT和癌症进展中的作用.
主要方法:
- 研究了AXL诱导的TANK结合激酶1 (TBK1) 的酸化.
- 评估了TBK1对AKT3的相互作用和酸化,这取决于mTORC1.1.
- 研究了AKT3在牛核积累和EMT标志物表达中的作用.
- 在人类胰腺管道腺癌组织中分析了AKT3和Snail的同定位.
- 评估了AKT3缺乏对小鼠模型转移的影响.
主要成果:
- AXL激活导致TBK1酸化和AKT3和Snail的下游激活.
- TBK1直接结合并化AKT3,一个依赖mTORC1复合物的过程.
- 激活AKT3促进了牛核积累,增强了EMT.
- 核AKT3和Snail在人类胰腺瘤中同定位,与糟糕的结果相关.
- 缺乏AKT3的小鼠胰腺癌细胞表现出减少的转移性传播.
结论:
- AXL-TBK1-AKT3-Snail轴是EMT诱导和癌症进展的关键途径.
- 核AKT3是侵略性胰腺癌的潜在生物标志物.
- 向AKT3是一个有前途的治疗策略,用于抑制侵袭性癌症的EMT.
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