循环瘤细胞集群形成DNA甲基化使转移播种
Sofia Gkountela1, Francesc Castro-Giner2, Barbara Maria Szczerba1
1Cancer Metastasis Laboratory, Department of Biomedicine, University of Basel and University Hospital Basel, 4058 Basel, Switzerland.
Cell
|January 12, 2019
概括
循环瘤细胞 (CTC) 通过特定的DNA甲基化变化促进癌症转移. 研究人员发现FDA批准的药物可以分解CTC, 提供一种抑制癌症传播的新策略.
科学领域:
- 癌症生物学
- 表观遗传学
- 转移研究
背景情况:
- 循环瘤细胞 (CTC) 集群与转移潜力增加有关.
- 对于CTC集群的生物特征和脆弱性还没有充分了解.
研究的目的:
- 调查单个CTC和CTC集群的DNA甲基化情况.
- 确定CTC集群的弱点和潜在的治疗目标.
主要方法:
- 来自乳腺癌患者和小鼠模型的单个CTC和CTC集群的全基因组DNA甲基化概况.
- 对FDA批准的化合物进行查,以确定影响CTC集群完整性的药物.
主要成果:
- 在CTC集群中表现出特定的低甲基化,用于结合干度和与增殖相关的转录因子 (例如OCT4,NANOG,SOX2).
- Na+/K+ ATPase 抑制剂被确定为将 CTC 集群分离成单细胞的化合物.
- CTC集群的解离导致DNA甲基化重塑和抑制转移.
结论:
- CTC 聚类与表观遗传变化有关,这些变化促进了干性和转移.
- 使用特定化合物,如Na+/K+ ATPase 抑制剂来向CTC集群,可以抑制癌症转移.
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