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增加HSF1表达将人类乳腺上皮细胞引导到一个介质细胞表现型

Natalia Vydra¹, Agnieszka Toma-Jonik¹, Patryk Janus¹

¹Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-102 Gliwice, Poland.

|October 28, 2023

概括

热冲击因子1 (HSF1) 影响乳腺细胞表型,在高水平上促进介质细胞特征,在降低时促进上皮细胞特征. HSF1也与三阴性乳腺癌的侵袭性相关.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

热冲击因子1 (HSF1) 是热冲击蛋白表达和细胞应激反应的关键调节者.
HSF1还在基本的细胞过程中发挥作用,包括生长,发育和瘤发生.
乳腺上皮细胞存在于从上皮细胞到介质细胞表型的频谱中,这是一种涉及发育和癌症的过渡.

研究的目的:

研究HSF1在调节非瘤源人类乳腺上皮细胞 (MCF10A,MCF12A) 表型中的作用.
评估HSF1水平对表皮细胞 (CDH1) 和介质细胞 (VIM) 标记物表达的影响.
探索HSF1水平与三阴性乳腺癌 (TNBC) 细胞的侵入性表型之间的相关性.

主要方法:

研究HSF1对MCF10A和MCF12A细胞系的影响,其内源性HSF1水平不同.
在乳腺上皮细胞系中操纵的HSF1水平 (下调和过度表达).
评估了细胞增殖,Matrigel中的球形形成,以及CDH1和VIM标记物的表达.
在TNBC细胞系中与侵入性相关的HSF1水平和测试的HSF1抑制剂 (DTHIB) 疗效.

主要成果:

低调HSF1降低了MCF10A的增殖和球形形成,但增加了MCF12A细胞中的CDH1表达.
在MCF10A细胞中HSF1过度表达导致CDH1降低,VIM增加和纤维细胞状形态.
HSF1水平与TNBC细胞的侵入性呈正相关性,而DTHIB抑制了它们的生长.

结论:

升高的HSF1水平在乳腺上皮细胞中促进介质细胞表型,而降低的HSF1则有利于上皮细胞表型.
HSF1涉及到乳腺结构的动态重塑.
HSF1代表了入侵性三阴性乳腺癌的潜在治疗标.

关键词:

这是一种HSF1抑制剂.表皮细胞到介质细胞的过渡.热冲击转录因子 1 的热冲击转录因子人类乳腺上皮细胞

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