类固醇受体联合激活剂1通过增强MMP-9促进人类肝细胞癌的侵入性
Zhangwei Tong1,2, Yong Zhang1, Peng Guo1
1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Journal of cellular and molecular medicine
|March 20, 2024
概括
类固醇受体协活性剂-1 (SRC-1) 通过增加MMP-9表达来促进肝细胞癌 (HCC) 转移. 抑制SRC-1可减少转移,为HCC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
- 癌症研究 癌症研究
背景情况:
- 已知类固醇受体联合激活剂-1 (SRC-1) 在各种癌症中起瘤性作用.
- 高SRC-1表达通过Wnt/β-catenin信号加速肝细胞癌 (HCC) 的进展.
- 在HCK转移中SRC-1的作用在很大程度上仍未被探索.
研究的目的:
- 研究SRC-1在HCC转移中的作用.
- 为了阐明SRC-1-介导的HCC转移的潜在分子机制.
- 评估SRC-1作为HCC干预的潜在治疗点.
主要方法:
- 在HCC细胞中进行SRC-1敲击实验 (体外和体内).
- 分析MMP-9表达和促进剂活性.
- 使用HCC患者队列 (GEO数据库) 的相关性研究.
- 用布法林治疗以评估其对SRC-1,MMP-9和转移的作用.
主要成果:
- 通过增加矩阵金属蛋白酶-9 (MMP-9) 表达,SRC-1促进HCC转移.
- 在实验室和体内,SRC-1倒置显著抑制了HCC细胞转移.
- SRC-1作为NF-κB和AP-1的协活性剂,增强了MMP-9促进剂的活性.
- 在HCC标本中SRC-1和MMP-9水平之间的正相关性;较高的水平与生存率较差有关.
- 布法林治疗减少了SRC-1表达,MMP-9水平和HCC转移.
结论:
- 通过MMP-9的上调调节,SRC-1是HCC转移的关键调节器.
- 针对SRC-1,例如Bufalin,为HCC提供了一个有希望的治疗策略.
- SRC-1和MMP-9是预测HCC患者结果的潜在生物标志物.
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