阿里尔碳化合物受体 (AhR) 在结肠细胞和瘤中发出信号
Stephen Safe1, Huajun Han2, Arul Jayaraman3
1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
概括
亚利碳化合物受体 (AhR) 在结肠癌中起到瘤抑制作用. 失去AhR会增强瘤生长和Wnt信号,而AhR的激活会抑制结肠瘤发生.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 基碳化合物受体 (AhR) 在癌症中具有复杂的作用,既起瘤促进作用,又起瘤抑制作用.
- 在结肠癌中,证据表明AhR主要作为瘤抑制剂起作用,特别是当被连接体激活时.
研究的目的:
- 用小鼠模型研究AhR在结肠瘤发生中的作用.
- 阐明AhR在结肠中的瘤抑制活性背后的机制.
主要方法:
- 在炎症诱导 (AOM/DSS) 和遗传 (APC/Kras) 结肠癌模型中利用了野生类型和AhR淘汰赛小鼠.
- 评估AhR损失对结肠干细胞,有机体形成,瘤生长和基因表达的影响.
- 采用单细胞转录学来分析结肠密室中的基因表达变化.
主要成果:
- 失去AhR显著增强了结肠干细胞的增殖,有机体生长和瘤形成.
- 缺乏AhR导致FOXM1表达和活性增加,促进瘤生长.
- AhR抑制了SOCS3的表达,从而增强了IL22介导的STAT3激活及其抗瘤作用.
- 在APC/Kras模型中,AhR损失促进了Wnt信号传递,导致结肠癌发生的增加.
结论:
- 亚利碳化合物受体 (AhR) 在结肠中起到瘤抑制作用.
- 艾哈的瘤抑制活性是通过抑制FOXM1和调节IL22/STAT3信号通路来调节的.
- 向AhR可能为结肠癌治疗提供治疗策略.
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