国际肿瘤学杂志 ›› 2021, Vol. 48 ›› Issue (9): 564-567.doi: 10.3760/cma.j.cn371439-20210517-00110

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靶向Neddylation修饰通路及通路抑制剂MLN4924的抗肺癌作用及其机制研究

朱峰, 王诗雯, 鲜敬荣, 刘越, 赵虎, 张艳梅()   

  1. 复旦大学附属华东医院检验科 200040
  • 收稿日期:2021-05-17 修回日期:2021-06-17 出版日期:2021-09-08 发布日期:2021-09-22
  • 通讯作者: 张艳梅 E-mail:15618653286@163.com
  • 基金资助:
    国家自然科学基金(81902380);国家高技术研究发展计划(863计划)(2015AA021107-019);上海市科学技术委员会科研计划(18411960600);上海市科学技术委员会科研计划(18411950800);上海市“医苑新星”青年医学人才培养资助计划(2019-72)

Research on the anti-lung cancer effects of targeted Neddylation modifying pathway and its inhibitor MLN4924 and its mechanism

Zhu Feng, Wang Shiwen, Xian Jingrong, Liu Yue, Zhao Hu, Zhang Yanmei()   

  1. Department of Clinical Laboratory, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
  • Received:2021-05-17 Revised:2021-06-17 Online:2021-09-08 Published:2021-09-22
  • Contact: Zhang Yanmei E-mail:15618653286@163.com
  • Supported by:
    National Natural Science Foundation of China(81902380);National High-tech R&D Program of China(863 Program)(2015AA021107-019);Scientific Research Project of Shanghai Science and Technology Commission(18411960600);Scientific Research Project of Shanghai Science and Technology Commission(18411950800);Shanghai "Rising Stars of Medical Talent" Youth Development Program, Outstanding Youth Medical Talents(2019-72)

摘要:

Neddylation修饰通路在肺癌中过度活化,可通过激活其底物CRL泛素连接酶活性诱导CRL抑癌蛋白底物降解,从而促进肺癌的发生发展。Neddylation修饰通路的小分子抑制剂MLN4924可以诱导肺癌细胞发生细胞周期阻滞、细胞凋亡和衰老,发挥抗肺癌作用。此外,通过靶向Neddylation修饰通路关键酶及其底物Cullin家族蛋白也可以抑制肺癌发生发展。

关键词: 肺肿瘤, 分子靶向治疗, Neddylation

Abstract:

Neddylation is overactivated in lung cancer, which promotes the development of lung cancer by activating its downstream CRL ubiquitin ligase and promoting the CRL tumor-suppressor protein substrate degradation. MLN4924, a small molecule inhibitor of Neddylation, plays an anti-lung cancer role by inducing cell cycle arrest, apoptosis and senescence. Furthermore, targeting the key enzymes of Neddylation and their substrates, Cullin family proteins, can inhibit the development of lung cancer.

Key words: Lung neoplasms, Molecular targeted therapy, Neddylation