PHRF1通过调节肠直肠癌 HCT116-p53细胞中的SOX4表达来促进细胞入侵
Hung-Wei Lin1, Ting-Wei Shih1, Adaobi Amanna2
1Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan, R.O.C.
Anticancer research
|November 29, 2023
概括
含有PHD和RING指域的蛋白1 (PHRF1) 通过调节Kras突变和p53损失的细胞中的SOX4表达来影响结直肠癌的侵袭. 这项研究揭示了PHRF1
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 众所周知,PHRF1 (PHD和RING指域含有蛋白1) 可以在任何地方化TGIP并增强TGF-β信号传递.
- 它在癌症侵袭中的作用,特别是在Kras突变和p53失活的背景下,仍然在很大程度上未被描述.
研究的目的:
- 为了研究PHRF1在结直肠癌细胞入侵中的功能.
- 确定PHRF1在存在瘤性Kras (KrasG13D) 和p53缺陷 (p53-/-) 的情况下对细胞入侵的影响.
主要方法:
- 使用CRISPR-Cas9基因编辑,在HCT116-p53-/- (KrasG13D/p53-/-) 大肠直肠癌细胞中淘汰PHRF1.
- 在PHRF1-淘汰细胞上进行表达概况和入侵试验.
主要成果:
- 与肺癌细胞不同,PHRF1淘汰并没有影响HCT116-p53-/-细胞中的Zeb1表达.
- 发现SOX4表达对于PHRF1-KNOCK-OUT HCT116-p53-/-细胞中观察到的受损入侵是关键的.
- PHRF1的C端SRI域对于入侵和SOX4表达至关重要;重新引入SOX4部分恢复了入侵.
结论:
- 在克拉斯突变,p53缺乏结直肠癌细胞的入侵中,PHRF1起着重要作用.
- 通过调节SOX4表达,PHRF1调节结直肠癌细胞的入侵.
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