白血病抑制因子调节纤维细胞生长因子受体4转录在胃癌中
Cristina Di Giorgio1, Rachele Bellini1, Antonio Lupia2,3
1Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Cellular oncology (Dordrecht, Netherlands)
|November 9, 2023
概括
白血病抑制因子 (LIF) 通过JAK1/STAT3信号调节胃癌中的纤维细胞生长因子受体4 (FGFR4). 抑制LIF或FGFR4可能为胃腺癌提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 胃腺癌 (GC) 是癌症死亡的主要原因,治疗选择有限.
- 纤维细胞生长因子受体 (FGFRs) 与癌症有关,其中FGFR4在H. pylori感染的GC中显示STAT3依赖调节.
- 准FGFR4为GC提供了一个潜在的治疗途径.
研究的目的:
- 为了确定调节FGFR4信号传递在胃癌中的因素.
- 探索GC中FGFR4的调节机制.
- 调查针对LIF/LIFR/FGFR4轴的治疗潜力.
主要方法:
- 对GC患者活检,患者衍生器官 (PDO) 和癌症细胞系的RNA测序分析.
- 研究了白血病抑制因子 (LIF) 和其受体 (LIFR) 在FGFR4调控中的作用.
- 使用LIFR抑制剂 (LIR-201) 和FGFR4抑制剂 (罗布利提尼布,siRNA) 来评估途径调节.
主要成果:
- FGFR4的表达和功能由LIF以JAK1/STAT3依赖的方式进行调节.
- 在GC患者队列中观察到LIFR和FGFR4表达之间的直接相关性.
- LIFR抑制取消了STAT3酸化和LIF诱导的致癌效应,FGFR4被确定为下游目标.
- 抑制FGFR4还降低了STAT3酸化,并废除了LIF的致癌作用.
- 治疗LIR-201抑制了FGF19的致癌潜力,这是FGFR4.4的生理连体.
结论:
- 通过GC中的LIF/LIFR通路发现了FGFR4的新型调节机制.
- 在胃癌细胞中,LIF和FGF19信号与瘤性STAT3的调节趋同.
- 这些发现突出了LIF/LIFR/FGFR4/STAT3轴作为GC的潜在治疗目标.
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