CCN1通过激活瘤干细胞中由S100A8调节的NF-κB信号通路来促进介质细胞表型过渡
Xing Guo1, Shuhua Guo2, Feng Tian2
1Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China.
CNS neuroscience & therapeutics
|December 11, 2024
概括
细胞通信网络因子1 (CCN1) 驱动着质母细胞干细胞的侵入性和介质细胞过渡,影响患者的预后. 向CCN1为质母细胞瘤 (GBM) 提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 癌症干细胞生物学
- 分子信号传输的方法
背景情况:
- 质瘤干细胞 (GSC) 和介质细胞表型过渡与质母细胞瘤 (GBM) 预后不佳有关.
- 细胞通信网络因子1 (CCN1) 与各种癌症有关,但其在GSC表型过渡和瘤发生性中的作用尚不清楚.
研究的目的:
- 研究CCN1在GSCs的表型转变和瘤性中的作用.
- 阐明CCN1影响GBM进展的潜在分子机制.
主要方法:
- 对TCGA和CGGA数据库的生物信息分析.
- 在体外测试包括表型验证,球体形成,ELDA和使用GBM和GSC模型的跨井测试.
- 高通量RNA-seq用于识别下游信号通路.
- 在体内研究使用内异种植GSC小鼠模型.
主要成果:
- CCN1在介酶性GBM/GSC中表达高,与预后不佳相关.
- CCN1 knockdown降低了MES-GSCs的茎度,增殖,入侵和瘤性;CCN1过度表达对PN-GSCs产生了相反的效果.
- CCN1激活了FAK/STAT3信号,对S100A8进行了上调,这反过来又使NF-κB/p65通路失活,抑制了瘤发生.
结论:
- 在GBM中,CCN1是GSC侵入性和介质细胞表型过渡的关键因素.
- 向CCN1为GBM治疗提供了一个有前途的治疗策略.
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