NM23-H1蛋白抗肿瘤转移的作用机制及治疗性应用

Tumor metastasis suppressor NM23-H1:functional pathway and therapeutic applications

目的对NM23-H1蛋白调节肿瘤细胞转移进程的作用机制进行综述,以加深对该类转移抑制基因(metastasis suppressors)的了解。方法对近几十年NM23-H1蛋白参与肿瘤进展相关的文章进行归纳和总结,分析该蛋白复杂的抗肿瘤转移机制。结果作为世界上第一个被鉴定的转移抑制基因,NM23-H1蛋白表达水平与肿瘤的侵袭和迁移能力呈负相关关系。其抗肿瘤转移机制复杂,除了和自身多样的酶活性有关外,复杂的蛋白相互作用网络以及对相关基因的转录调控作用都与其抗肿瘤机制密切相关。结论尽管恶性转移肿瘤中NM23-H1低表达的机理仍然未知,但增加它翻译水平抑制肿瘤迁移的研究已经进入临床试验阶段,基于NM23-H1开展的治疗手段有不错的应用前景。

Objective The mechanism of NM23-H1 protein in regulating tumor cell metastasis was reviewed to deepen the understanding of this type of metastasis suppressors.Methods The articles related to the involvement of NM23-H1 protein in tumor progression were summarized in recent decades,and the complex anti-tumor metastasis mechanism of this protein was analyzed.Results As the first identified metastasis suppressor in the world,the expression level of NM23-H1 protein was negatively correlated with tumor invasion and migration ability.The mechanisms underlying the anti-metastatic properties of NM23-H1 were complex,which involved its various enzymatic activities,protein-protein interactions,and the related genes regulation.Conclusion Although the mechanism of low expression of NM23-H1 in malignant metastatic tumors remains unclear,the approaches of boosting NM23-H1 expression at the translational level have already been tested in the clinic trials,and the therapeutic methods based on NM23-H1 have good application prospects.