通过表皮细胞到介质细胞的可塑性,对瘤性RAS进行合作性亲瘤原生适应
Hadrien De Blander1,2, Laurie Tonon3, Frédérique Fauvet1,2
1Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue Contre le Cancer, 69008, Lyon, France.
Science advances
|February 14, 2024
概括
乳腺细胞中的瘤性RAS激活驱动了表皮细胞到介质细胞的可塑性 (EMP) 和恶性转变. 这个过程是由衰老细胞的炎症性细胞因子推动的,挑战瘤抑制作用.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 乳腺癌中异常RAS/MAPK通路的激活与介质细胞和干性特征相关.
- 这表明RAS/MAPK信号传递与上皮细胞到介质细胞可塑性 (EMP) 之间存在联系.
研究的目的:
- 研究瘤性RAS激活在促进EMP和人类乳腺上皮细胞恶性转变中的作用.
- 阐明RAS信号影响细胞衰老和EMP的机制.
主要方法:
- 利用人类乳腺上皮细胞的诱导模型.
- 通过瘤性RAS.分析了ZEB1-依赖的EMP诱导.
- 研究了由衰老细胞分泌的促炎细胞因子IL-6和IL-1α的作用.
主要成果:
- 瘤性RAS激活促进了ZEB1依赖的EMP,这对恶性转变至关重要.
- EMP是由邻近的RAS激活衰老细胞的促炎细胞因子 (IL-6,IL-1α) 触发的.
- 数据挑战了老化仅仅是瘤抑制的观点,而EMP仅仅是晚期进展因素.
结论:
- 被RAS激活的乳腺上皮细胞表现出促瘤的合作.
- 这种合作利用基因诱导衰老和EMP进行细胞重编程和恶性转变.
- 突出了衰老和EMP在乳腺癌早期发展中的新型前瘤作用.
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