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矛盾的是,EMT因子ZEB1在BRAF突变癌瘤中抑制EMT

Ester Sánchez-Tilló^1,2,3, Leire Pedrosa⁴, Ingrid Vila¹

¹Group of Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer, Department of Oncology and Hematology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

|October 23, 2023

概括

在基于KRAS或BRAF突变的结直肠癌进展中,ZEB1具有相反的作用. 在KRAS突变瘤中,ZEB1使预后恶化,而在BRAF突变瘤中,它改善了结果并减少了转移.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症遗传学癌症遗传学

背景情况:

具有KRAS和BRAF突变的结肠直肠癌 (CRC) 呈现出不同的进展模式.
众所周知,ZEB1诱导了表皮细胞转移到介质细胞转移 (EMT),并且经常与各种癌症的预后不佳有关.

研究的目的:

研究ZEB1在KRAS突变与BRAF突变结直肠癌中的对比功能.
阐明ZEB1对瘤进展和转移的差异影响的机制基础.

主要方法:

对患者的CRC样本和KrasG12D/BrafV600E小鼠模型的分析.
使用Zeb1缺乏的小鼠进行功能研究.
评估了EMT,增殖,生存和ERK信号的基因表达特征.
进行ZEB1敲击实验以评估细胞表型.

主要成果:

在KRAS突变的CRC中,ZEB1与更差的预后和增加的EMT相关.
在BRAF突变CRC中,ZEB1与更好的预后,减少EMT和更少的转移有关.
在KRAS与BRAF突变CRC细胞中,ZEB1与EMT,增殖,存活和ERK信号基因签名的相关性相反.

结论:

ZEB1在CRC中表现出上下文依赖的作用,在KRAS突变瘤中充当瘤基因,在BRAF突变瘤中充当瘤抑制剂.
这些发现强调了在考虑ZEB1或EMT向治疗时,CRC中KRAS/BRAF突变状态的关键重要性.

关键词:

结肠直肠癌是一种癌症.胃肠病学胃肠病学在瘤学瘤学.

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