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VGLL4通过Wnt/β-catenin通路促进肝细胞癌的进展
Gaoxiong Wang1, Zhiwei Chen2, Juanyong Pan3
1Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian, China; Department of General Surgery, Quanzhou Maternal and Child Health Care Hospital, Quanzhou, Fujian, China; College of Medicine, Huaqiao University, Quanzhou, Fujian, China.
在肝细胞癌 (HCC) 中,VGLL4的调节升高,促进瘤生长,入侵和茎状. 这种蛋白质作为预后生物标志物和HCC的潜在治疗标,将瘤进展与Wnt/β-catenin信号传递和 stromal 相互作用联系起来.
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:
- 肝细胞癌 (HCC) 是一个重大的临床挑战,因为诊断迟到,治疗选择有限.
- 了解推动HCC进展的分子机制对于开发有效疗法至关重要.
研究的目的:
- 研究VGLL4在肝细胞癌 (HCC) 进展中的作用和作用机制.
- 评估VGLL4作为潜在的预后生物标志物和HCC的治疗点.
主要方法:
- 从癌症基因组图谱 (TCGA) 队列 (355名HCC患者,43名对照) 的RNA-seq数据和临床信息的分析.
- 在体外实验中使用HuH-7 HCC细胞来评估VGLL4过度表达后的增殖,迁移,入侵和干细胞.
- 在体内皮下异种移植小鼠模型中,评估VGLL4对瘤生长的影响.
主要成果:
- 在HCC瘤中,VGLL4显著上调,表达与TNM阶段正相关.
- 高VGLL4表达独立预测了较短的整体和无进展生存期,并显示出诊断价值.
- 在体外,VGLL4过度表达增强了HCC细胞的增殖,迁移,入侵和干细胞,并在体内增加了瘤的生长.
- 从机制上讲,VGLL4激活了Wnt/β-catenin通路,诱导了上皮层-介质细胞过渡 (EMT),并与肌体细胞 (CAF,MDSC,巨细胞,内皮细胞) 的透增加相关.
结论:
- VGLL4通过将瘤内在的EMT/stemness程序与通过Wnt/β-catenin通路的 stromal crosstalk集成来驱动HCC的进展.
- VGLL4作为一个有价值的预后生物标志物和肝细胞癌的潜在治疗点.
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