School of Clinical and Basic Medical Sciences, Shandong First Medical University, Jinan, Shandong 250117, P.R. China.
Department of Thoracic Surgery, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China.
Int J Oncol. 2024 Apr;64(4). doi: 10.3892/ijo.2024.5627. Epub 2024 Feb 23.
Neddylation, akin to ubiquitination, represents a post‑translational modification of proteins wherein neural precursor cell‑expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8‑mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti‑CRC target.
类泛素化修饰类似于泛素化修饰,是一种蛋白质翻译后修饰方式,在此过程中,神经前体细胞发育下调蛋白 8(NEDD8)通过一系列反应修饰在底物蛋白上。类泛素化修饰在动物细胞的生长和增殖中起着关键作用。在结直肠癌(CRC)中,它主要促进肿瘤细胞的增殖、转移和存活,降低患者的总生存率。通过调节癌细胞内的多种生物学反应,如 DNA 损伤反应和细胞凋亡等,对 NEDD8 介导的类泛素化途径进行策略性的操纵,在调节肿瘤生长方面具有巨大的治疗潜力。MLN4924 是一种 NEDD8 的抑制剂,与铂类药物和伊立替康联合使用,以及通过药物再利用筛选的周期抑制剂和 NEDD 激活酶抑制剂,已被发现具有有前途的抗肿瘤作用。本综述总结了近年来对 NEDD8 在 CRC 进展中的作用的理解进展,表明 NEDD8 是一个有前途的抗 CRC 靶点。