通过调节Hippo-YAP信号通路,PKC-eta促进乳腺癌转移
Vijayasteltar B Liju1, Kamran Waidha1, Amitha Muraleedharan1,2
1The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
蛋白激酶C-eta (PKCη) 通过Hippo通路激活YAP驱动三阴性乳腺癌 (TNBC) 转移. 一种新降解PKCη,抑制转移并为TNBC提供潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 三重阴性乳腺癌 (TNBC) 是具有不良预后的侵袭性.
- 蛋白激酶C-eta (PKCη) 与乳腺癌的不良结果和转移有关.
- 在TNBC中,PKCη表达与上皮-介质细胞过渡 (EMT) 相对应.
研究的目的:
- 研究PKCη在TNBC转移中的作用.
- 阐明PKCη促进转移的分子机制.
- 确定TNBC的潜在治疗点.
主要方法:
- 基因废除研究 (PKCη-Knockout细胞).
- 在NSG小鼠中的正位素异种移植模型.
- 对Hippo通路信号的分析 (YAP,AKT).
- 从上游开放阅读框架 (uORF) 中识别PKCη降解.
主要成果:
- 通过增强EMT和干度,PKCη促进TNBC转移.
- PKCη通过抑制Hippo通路来激活YAP,从而导致YAP稳定和核转位.
- PKCη对AKT进行负面调节,进一步降低Hippo通路的调节.
- 一个uORF编码的降解PKCη,激活Hippo路径和YAP降解,从而减少转移.
结论:
- PKCη通过调节Hippo-YAP通路的信号轴驱动TNBC转移.
- 准PKCη或其上游监管机构为TNBC提供了潜在的治疗策略.
- 这种uORF编码的提供了一种新的方法来抑制TNBC中的PKCη和YAP活性.
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