在黑色素瘤进展中,YAP1控制了N-cadherin介导的瘤-肌瘤相互作用
Yao Xiao1, Linli Zhou1, Thomas Andl2
1Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267, USA.
流体的YAP1 (Yes-associated protein 1) 信号调节了黑色素瘤中的卡德林切换. 癌症相关纤维细胞 (CAF) 中的YAP1驱动N-cadherin的表达,通过PI3K-AKT信号传递促进黑色素瘤的进展.
科学领域:
- 癌症生物学 癌症生物学
- 细胞信号传递 细胞信号传递
- 瘤微环境 瘤微环境
背景情况:
- 在黑色素瘤中,上皮细胞转换为介质细胞转换 (EMT) 涉及从E-cadherin转换为N-cadherin.
- 黑色素瘤细胞与树皮纤维细胞形成N-cadherin粘附,但调节不清楚.
研究的目的:
- 调查 stromal Yes-associated protein 1 (YAP1) 在调节黑色素瘤中的卡德林切换中的作用.
- 阐明YAP1信号影响黑色素瘤进展的机制.
主要方法:
- 利用了一个BRAF突变小鼠黑色素瘤模型.
- 在癌症相关纤维细胞 (CAFs) 中进行了YAP1切除和过度表达.
- 采用RNA测序 (RNA-Seq) 来识别下游效应因子.
主要成果:
- 在CAF中YAP1消去抑制了黑色素瘤的进展;YAP1过度表达加速了它.
- N-cadherin被确定为CAF中YAP1的一个关键下游效应因子.
- 在CAF中抑制YAP1降低了黑色素瘤细胞中的N-cadherin,抑制PI3K-AKT信号和扩散.
结论:
- 流体YAP1信号传递是黑色素瘤中N-cadherin介导相互作用的关键调节器.
- 在CAF中准YAP1可以破坏瘤-肌瘤通信,并逆转黑色素瘤的侵入性.
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