USP21-EGFR信号轴在功能上与转移性结直肠癌有关
Ji Hye Shin1, Mi-Jeong Kim1, Ji Young Kim1
1Department of Immunology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Cell death discovery
|December 18, 2024
概括
乌比基特异性酶21 (USP21) 通过稳定EGFR. 促进结直肠癌 (CRC) 转移. 用BAY-805抑制USP21减少了瘤生长,这表明USP21是转移性CRC的治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移 癌症转移
背景情况:
- 乌比基特异性酶21 (USP21) 稳定了Fra-1 (FOSL1),促进了结直肠癌 (CRC) 的转移.
- 通过矩阵金属蛋白酶 (MMPs) 的EGFR信号传递和Fra-1激活之间存在联系.
- 在转移性CRC (mCRC) 中USP21-EGFR轴的作用需要进一步阐明.
研究的目的:
- 在mCRC患者中研究USP21和EGFR表达之间的临床相关性.
- 阐明USP21-EGFR信号轴在CRC进展和转移中的功能作用.
- 评估USP21抑制在mCRC中的治疗潜力.
主要方法:
- 来自27名mCRC患者的瘤和正常组织的RNA测序分析.
- 通过CRISPR/Cas9介导生成USP21-Knockout (USP21-KO) 的CRC细胞.
- 在体外和体内测试,包括NSG小鼠的增殖,迁移,殖民地形成,3D瘤球形形成和异种移植模型.
- 对USP21抑制剂BAY-805.5的评估
主要成果:
- 增加USP21和EGFR表达与mCRC患者的生存率较差相关.
- USP21通过脱化增强了EGFR的稳定性,减少了EGFR的降解.
- USP21-KO CRC 细胞显著减少了繁殖,迁移,殖民地形成和球形形成.
- 在体内,USP21-KO细胞表现出瘤发生活性降低.
- 在CRC细胞中,BAY-805抑制了EGF刺激的3D瘤球状体的形成.
结论:
- 通过稳定EGFR,USP21在促进mCRC进展和转移方面发挥着关键作用.
- 抑制USP21代表了对mCRC的有前途的治疗策略.
- USP21可以作为EGF驱动的mCRC的有价值的预测生物标志物.
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