JMJD5通过促进EGFR蛋白质体降解来抑制肺癌的进展
Jing Shen1, Guiling Liu2, Hongyan Qi3
1Department of Pathology and Pathophysiology, and Department of Medical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. shenjingwzy@zju.edu.cn.
Cell death & disease
|October 9, 2023
概括
减少JMJD5表达促进非小细胞肺癌 (NSCLC) 的生长. JMJD5破坏了表皮生长因子受体 (EGFR) 的稳定,抑制了NSCLC的进展,克服了TKI耐药性.
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:
- 异常的表皮生长因子受体 (EGFR) 信号驱动非小细胞肺癌 (NSCLC) 的发展.
- EGFR氨酸激酶抑制剂 (TKI) 受到抗性突变的挑战.
研究的目的:
- 研究JmjC域含有5 (JMJD5) 在NSCLC中的作用.
- 确定JMJD5在调节EGFR稳定性和TKI抗性的机制.
主要方法:
- 评估了与EGFR稳定性和NSCLC进展有关的JMJD5表达.
- 解析了JMJD5与E3结合酶HUWE1的相互作用,用于EGFR蛋白质体降解.
- 研究了JMJD5通过细胞外囊泡进行的细胞间传输.
主要成果:
- 减少JMJD5表达与EGFR稳定性增加和NSCLC进展相关.
- JMJD5通过HUWE1和蛋白质体降解来破坏野生型EGFR和TKI耐药突变的稳定性.
- 细胞外囊泡介导的JMJD5传输抑制了NSCLC的生长.
结论:
- 在NSCLC中,JMJD5通过破坏EGFR的稳定而起瘤抑制作用.
- 针对JMJD5降解EGFR是一种潜在的治疗策略,用于EGFR突变的NSCLC和TKI耐药性.
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