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FOXF1促进瘤血管的正常化,并通过FZD4预防肺癌的进展
Fenghua Bian1, Chinmayee Goda1, Guolun Wang1
1Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA.
EMBO molecular medicine
|April 8, 2024
概括
叉头盒F1 (FOXF1) 调节癌症中的肺内皮细胞重编程. 恢复FOXF1或FZD4的表达正常化瘤血管,抑制非小细胞肺癌的进展.
科学领域:
- 在瘤学瘤学.
- 血管生物学 血管生物学
- 分子生物学分子生物学
背景情况:
- 癌细胞将正常的肺内皮细胞 (EC) 重编程为与瘤相关的内皮细胞 (TEC).
- TEC形成漏水血管,支持瘤生长和转移.
- 对于EC-to-TEC重编程的转录调节器,大部分是未知的.
研究的目的:
- 确定EC到TEC过渡的转录调节者.
- 研究叉头盒F1 (FOXF1) 在非小细胞肺癌 (NSCLC) 中的作用.
- 探索向FOXF1或其下游途径的治疗潜力.
主要方法:
- 在NSCLC组织中评估FOXF1表达,与患者存活率相关.
- 使用了具有内皮特异性FOXF1缺失或过度表达的小鼠模型.
- 研究了FOXF1对Wnt/β-catenin信号传递和Fzd4表达的调节.
- 在体内使用纳米粒子介导的Fzd4cDNA输送.
主要成果:
- 在TEC中,FOXF1的表达减少,并与NSCLC患者的生存率低下有关.
- 在小鼠中,内皮特异性FOXF1缺失增加了血管泄漏,缺氧,并促进了瘤生长/转移.
- 过度表达FOXF1使瘤血管正常化,并抑制了肺癌的进展.
- 缺少FOXF1会通过降低Fzd4.4的调节来降低Wnt/β-catenin信号传递.
- 纳米粒子输送Fzd4cDNA拯救了信号传输,使血管正常化,并抑制了瘤的进展.
结论:
- FOXF1是EC-TEC过渡的关键调节者,促进瘤血管的稳定性.
- 在TEC中,FOXF1通过增强FZD4/Wnt/β-catenin信号传递来抑制NSCLC的进展.
- 针对FOXF1或FZD4,可能通过纳米粒子输送,显示了NSCLC的治疗前景.
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