通过Ck2控制和Src/Akt/Stat3减弱,Mcam通过Ck2控制和Src/Akt/Stat3减弱来稳定发光原始乳腺癌表型
Ozlen Balcioglu1,2, Brooke L Gates1,2, David W Freeman1,2
1Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112 USA.
bioRxiv : the preprint server for biology
|April 2, 2024
概括
通过调节Ck2信号传递,Mcam蛋白控制乳腺癌细胞的可塑性和避开他莫西芬治疗. Mcam knockdown 抑制了瘤生长和侵略性的细胞状态过渡.
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:
- 乳腺癌亚型是由受体表达和基因模式定义的,影响治疗和预后.
- 瘤细胞的可塑性允许适应治疗和进展.
- 在乳腺癌细胞状态控制和瘤性中Mcam的作用需要进一步研究.
研究的目的:
- 调查Mcam在调节乳腺癌细胞状态,血统可塑性和瘤性方面的功能.
- 探索Mcam影响信号通路和治疗反应的分子机制.
- 评估Mcam对瘤生长和侵袭性细胞表型 in vitro 和 in vivo 的影响.
主要方法:
- 使用了一种类似于光原体的小鼠乳腺癌细胞系 (Py230) 具有固有的血统可塑性.
- 进行了Mcam淘汰实验,以评估对细胞信号,形态,迁移和基因表达的影响.
- 研究了Mcam和Ck2 (酶二酶) 之间的相互作用及其在调节Stat3和Pi3K/Akt等信号通路中的作用.
- 在体内评估瘤生长,转移和细胞状态转变.
主要成果:
- 在Py230细胞中,Mcam的淘汰导致了Stat3和Pi3K/Akt的激活,将细胞状态从激素感应的光原体转移到对他莫西芬耐药的基础表型.
- Mcam结合Ck2并调节其基质利用,影响细胞形态,迁移和粘附信号.
- 在体内,Mcam knockdown降低了瘤生长,抑制了侵略性的神经状细胞过渡,并降低了瘤增长率.
- 人类光线乳腺癌显示了与Cyclin D放大和积极的Luminal B亚型相关的MCAM复制数损失.
结论:
- 在控制乳腺癌细胞状态可塑性和逃避向疗法的过程中,Mcam发挥着至关重要的作用.
- Mcam对Ck2的调节是影响瘤进展和治疗耐药性的关键机制.
- 向Mcam或Ck2可能为乳腺癌的联合治疗提供新的策略.
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