通过激活Notch信号通路,AGRN促进肺腺癌的进展,并作为治疗点
Huan Zhang1, Jiaqi Liang2, Tao Lu2
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; Division of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China.
亚格林 (AGRN) 在肺腺癌 (LUAD) 中被上调,通过NOTCH1通路促进瘤生长和转移. 抗AGRN抗体对LUAD治疗具有治疗潜力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 肺腺癌 (LUAD) 是全球癌症死亡的主要原因.
- 农林 (AGRN) 在LUAD发展中的作用和机制尚不清楚.
研究的目的:
- 为了研究AGRN在LUAD中的表达,功能和机制.
- 评估在LUAD中准AGRN的治疗潜力.
主要方法:
- 单细胞RNA测序和免疫组织化学用于AGRN表达分析.
- 对120名LUAD患者进行回顾性研究,以将AGRN表达与临床结果相关联.
- 在体外和体内实验中评估AGRN对LUAD细胞行为和瘤生长的影响.
- 研究AGRN与NOTCH1的相互作用及其下游通路激活.
- 开发和测试抗AGRN抗体.
主要成果:
- 在LUAD中,AGRN表达显著上调.
- 高AGRN表达与淋巴结转移和LUAD患者的不良预后相关.
- AGRN与NOTCH1直接相互作用,激活了NOTCH通路.
- AGRN促进LUAD细胞的增殖,迁移,入侵,上皮-介质细胞过渡 (EMT) 和瘤发生.
- 阻止NOTCH通路可以逆转AGRN介导的效应.
- 反AGRN抗体治疗抑制了LUAD的增殖,并诱导了亡.
结论:
- AGRN 在 LUAD 发育和通过 NOTCH1 途径的进展中发挥着关键作用.
- 用抗体向AGRN是LUAD的一种有前途的治疗策略.
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