卡德林介导接触正常化对瘤性Src酶介导基因表达和蛋白质酸化的影响
Rachel E Nicoletto1, Cayla J Holdcraft1, Ariel C Yin1
1Rowan-Virtua School of Osteopathic Medicine, Rowan University, B330 Science Center, 2 Medical Center Dr., Stratford, NJ, 08084, USA.
Scientific reports
|October 13, 2024
概括
正常和癌细胞之间的接触正常化通过抑制Wnt信号抑制瘤生长. 这个过程调节瘤激酶活性和基因表达,影响癌症的进展.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子瘤学分子瘤学
背景情况:
- 非转化细胞通过与转化细胞的卡德林结合抑制瘤生长,这一过程被称为"接触正常化".
- 转变的细胞必须克服接触正常化以入侵和转移,需要异细胞干结.
- 在接触正常化中,德林信号的下游机制尚不清楚.
研究的目的:
- 调查接触正常化是否影响转化细胞中的Wnt信号传递.
- 阐明接触正常化对癌细胞中基因表达和蛋白质酸化的下游影响.
主要方法:
- 在Src转化小鼠胚胎细胞中使用β-catenin记者结构 (GFP).
- 采用了基因表达 (RNA-Seq) 和蛋白质组分析的分层培养系统.
- 研究卡德林能力和瘤性Src酶活性所产生的影响.
主要成果:
- 接触正常化减少了与合格的非转化细胞培养的转化细胞中的β-catenin驱动的GFP表达.
- RNA-Seq显示了Src诱导的转录的抑制和通过接触正常化激活Src抑制的转录.
- 蛋白质组分析显示,接触正常化后关键蛋白质的氨酸酸化降低.
结论:
- 卡德林依赖的接触正常化抑制了转化细胞中的Wnt信号传递.
- 这种抑制调节瘤性激酶活性和基因表达,包括PDPN.
- 接触正常化作为一种控制瘤进展的机制.
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