阿尔法-胎蛋白通过LATS2/YAP/TEAD1途径上调肝细胞癌细胞内在PD-1表达
Guangxian Leng1, Hongxia Gong2, Guiyuan Liu3
1Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China.
阿尔法-胎蛋白 (AFP) 通过增加编程死亡1 (PD-1) 表达来驱动肝细胞癌 (HCC) 的进展. AFP激活了LATS2/YAP/TEAD1通路,促进了HCC细胞中的PD-1转录.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 肝细胞癌 (HCC) 的进展与细胞内在编程死亡1 (PD-1) 有关.
- 在HCC中调节PD-1表达的机制在很大程度上是未知的.
- 这项研究探讨了α-fetoprotein (AFP) 在调节HCC细胞PD-1表达中的作用.
研究的目的:
- 为了研究α-fetoprotein (AFP) 对肝细胞癌 (HCC) 细胞内在编程死亡1 (PD-1) 表达的调节作用.
- 阐明在HCC中连接AFP和PD-1的潜在分子机制.
主要方法:
- 定量实时PCR和西部抹迹来评估PD-1和AFP的表达.
- 同免疫沉 (CO-IP) 用于识别与AFP相互作用的蛋白质.
- 染色体免疫沉 (ChIP) 和双酶记者测定证实TEAD1与PD-1促进体结合.
主要成果:
- 在HCC细胞内在PD-1表达和AFP水平之间观察到正相关性.
- 发现AFP可以抑制大型瘤抑制剂2 (LATS2) 和是相关蛋白 (YAP) 的酸化.
- 通过AFP抑制LATS2/YAP酸化导致YAP核转位,通过TEAD1.1促进PD-1转录.
结论:
- 阿尔法-胎蛋白 (AFP) 作为肝细胞癌 (HCC) 细胞内在PD-1的上游调节剂.
- 在LATS2/YAP/TEAD1信号轴中介于HCC中AFP诱导的PD-1上调.
- 这些发现提供了对HCC病原体和潜在治疗点的见解.
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