在结直肠癌转移中的表型异质性和可塑性
Samuel Ogden1, Nasrine Metic1, Ozen Leylek1
1Barts Cancer Institute, Queen Mary University of London, London, UK.
Cell genomics
|May 20, 2025
概括
这项研究揭示了结直肠癌 (CRC) 细胞如何改变和扩散. 关键的调节器AP-1和NF-κB推动了这些变化,为阻止转移提供了潜在的新目标.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 大肠直肠癌 (CRC) 呈现现型异质性,这对于瘤进展,转移和治疗耐药性至关重要.
- 驱动CRC中这种异质性的特定监管因素和外部信号在很大程度上仍未确定.
研究的目的:
- 为了研究分子驱动因素和信号通路,在结直肠癌的表型异质性背后.
- 识别特定的癌细胞状态及其促进转移的调节机制.
主要方法:
- 在原发性和转移性CRC患者样本上利用单细胞多组学和空间转录学.
- 集成的多omics数据来识别不同的癌细胞表型和它们的空间组织.
- 分析了转录因子活性和配体受体相互作用.
主要成果:
- 识别了具有再生和炎症表型的癌细胞状态,类似于转移启动细胞.
- 发现了一个中间的混合再生和干细胞表型群体.
- 揭示了转录因子AP-1和NF-κB作为这些表型的关键调节者.
- 在侵袭性边缘和肝转移的免疫抑制利基内定位这些细胞状态.
- 发现了促进再生和炎症表型的特定体受体相互作用.
结论:
- 在CRC中的表型异质性是由特定的转录因子 (AP-1,NF-κB) 和信号通路调节的.
- 这些调节因素和途径有助于形成转移启动细胞状态.
- 针对这些已识别的调节和信号因子,为抑制结直肠癌转移提供了潜在的治疗策略.
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