科斯塔丁M通过HIF1A激活调节集体上皮质迁移
Ian C McLean1, Sean M Gross1,2, Tiera A Liby1
1Department of Biomedical Engineering, OHSU, Portland, OR USA.
bioRxiv : the preprint server for biology
|October 3, 2025
概括
Kostatin M (OSM) 通过激活缺氧诱导因子-1 (HIF1A) 来驱动集体细胞迁移 (CCM),这重编程细胞行为并影响癌症的进展. 这种细胞因子介导的途径在人类瘤中活跃.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 细胞外信号极大地影响细胞行为,但结合体介导的表型变化的机制尚不清楚.
- 康斯塔丁M (OSM) 是一种细胞因子,涉及到平衡,伤口愈合,炎症和癌症.
- 在乳腺上皮细胞中,OSM诱导集体细胞迁移 (CCM),细胞在那里凝聚力地移动.
研究的目的:
- 研究OSM驱动CCM的机制.
- 为了比较OSM与表皮生长因子 (EGF) 和干扰素玛 (IFNG) 的作用.
- 定义涉及OSM诱导的CCM的联体特异性表型和分子网络.
主要方法:
- 综合性转录组和蛋白组分析.
- 确定分子调节剂的功能验证.
- 对OSM,EGF和IFNG信号通路的比较.
主要成果:
- 催氧诱导因子-1 (HIF1A) 和信号传感器和转录激活器3 (STAT3) 被确定为OSM反应的中央调节者.
- HIF1A激活驱动与缺氧,代谢重编程和免疫路径相关的转录程序.
- 补充信号作用于HIF1A的下游,其抑制会破坏OSM诱导的集群和CCM.
结论:
- 建立了OSM信号,HIF1A激活和CCM之间的机制联系.
- 由细胞因子驱动的转录重编程协调上皮细胞迁移.
- 确定的途径在人类乳腺瘤中活跃,可能在转移中发挥作用.
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