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CASP8AP2 / FLASH在调节表皮细胞到介质细胞过渡可塑性 (EMP) 中的双重作用

Madison Catalanotto¹, Joel Markus Vaz², Camille Abshire³

¹LSU Health Shreveport, School of Medicine, LA, USA.

Translational oncology

|November 20, 2023

概括

癌细胞中FLASH的丧失促进了杂交的上皮/甲细胞 (E/M) 现型,这对于癌症的入侵和转移至关重要. 这一发现强调了FLASH作为癌症上皮质可塑性的关键调节者.

科学领域:

癌症生物学癌症生物学
细胞可塑性细胞可塑性
分子瘤学分子瘤学

背景情况:

皮质到介质细胞的过渡 (EMT) 驱动癌症的进展,入侵和转移.
EMT可塑性 (EMP) 允许癌细胞在动态的微环境中适应和生存.
了解EMP的调节者对于开发向癌症疗法至关重要.

研究的目的:

调查质子调节剂FLASH,NPAT和SLBP在调节EMT可塑性的作用.
确定FLASH枯竭对癌细胞表型和基因表达的影响.
为了将癌细胞系中的FLASH表达与EMT标记者相关联.

主要方法:

RNA测序 (RNAseq) 用于分析全基因组的转录变化.
定量PCR和西部黑斑用于mRNA和蛋白质水平检测.
对基因表达的计算分析,以计算表皮和介质细胞分数.

主要成果:

即使在TGFβ刺激下,FLASH消耗还会诱导具有高表皮分数的混合E/M表型.
FLASH作为表皮表型的抑制剂,其表达与表皮评分相反相关.
在FLASH,NPAT或SLBP耗尽后,特定的间酶体标记被上调.

结论:

闪光消耗驱动一种混合的E/M表型,其特点是共存的上皮和介质细胞标记物 (ZEB1low/SNAILhigh/E-cadherinhigh).
这种混合的EM状态有助于癌细胞的生存和攻击性特征.
在癌症中,FLASH是EMT可塑性和表皮表型维护的关键调节者.

关键词:

卡斯巴酶8相关蛋白2 (CASP8AP2/FLASH) 是一种与卡斯巴酶8相关的蛋白.在EMT转录因子 (EMT-TFs) 中.皮质到介质细胞的转变 (EMT)

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