脂肪1删除促进混合EMT状态,瘤干和转移
Ievgenia Pastushenko1,2,3, Federico Mauri1, Yura Song1
1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Nature
|December 17, 2020
概括
FAT1基因功能损失通过促进混合上皮细胞转化为介质细胞转化 (EMT) 状态加速癌症. 这影响了瘤的发病,进展和转移,在缺乏FAT1的癌症中揭示了新的治疗脆弱性.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- 在人类癌症中,FAT1经常发生突变.
- FAT1突变在瘤发生中的确切作用和分子机制尚不清楚.
研究的目的:
- 研究FAT1在瘤开始和进展中的作用.
- 阐明FAT1在癌症发展中的作用的分子机制.
主要方法:
- 使用皮肤状细胞癌和肺瘤的小鼠模型.
- 进行了转录,染色体和蛋白质分析.
- 进行了机理学研究以确定关键的分子途径.
主要成果:
- 在小鼠模型中,脂肪1的删除加速了瘤的开始,进展和转移.
- 在小鼠和人类癌症中观察到一种混合的上皮细胞转化为介质细胞转化 (EMT) 现型.
- 失去FAT1功能会激活促进YAP1和ZEB1的CAMK2-CD44-SRC轴,同时不激活EZH2以调节SOX2,驱动混合EMT状态.
- 在缺乏FAT1的瘤中发现药物耐药性和脆弱性.
结论:
- 通过状细胞癌的混合EMT状态,FAT1功能的丧失促进了瘤的发病,进展,侵入性和转移.
- 了解这些机制可以为缺乏FAT1的癌症提供治疗策略.
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