蛋白磷酸酶2A与肿瘤发生发展关系的研究进展  

Research progress in relationship between protein phosphatase 2A and occurrence and development of tumor

作　　者：张慧灵 郭文秀 孟峻[1] ZHANG Huiing;GUO Wenxiu;MENG Jun(Department of Laboratory,Affiliated Hospital,Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学附属医院检验科,内蒙古呼和浩特010050

出　　处：《吉林大学学报(医学版)》2025年第2期534-540,共7页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金项目(81360109,81660267);内蒙古自治区科技厅自然科学基金项目(2021MS08158)。

摘　　要：蛋白磷酸酶2A (PP2A)是哺乳动物细胞中主要的丝氨酸-苏氨酸蛋白磷酸酶之一,在调控细胞有丝分裂和蛋白质去磷酸化等生物学活动中起重要作用。PP2A是一种肿瘤抑制因子,已被证实在多种实体肿瘤和白血病中存在基因改变或失活的现象,其活性受到抑制,从而促进肿瘤细胞不断增殖。临床研究表明:内源性抑制剂如SET、PP2A癌症抑制剂(CIP2A)和蛋白磷酸酶甲基酯酶-1(PME-1)等可降低PP2A活性,该过程被视为肿瘤恶化或复发的重要标志。而PP2A激活药物(如FTY720)可通过改变抑制剂SET的结构,恢复PP2A的肿瘤抑制活性,从而有效抑制肿瘤发展。因此,PP2A及其抑制剂可能成为临床上的潜在治疗靶点。现对PP2A及其抑制剂在恶性肿瘤发病中的作用机制及其在肿瘤治疗领域的应用进行全面综述,旨在为恶性肿瘤的治疗提供新方向。Protein phosphatase 2A(PP2A)is one of the major serine-threonine protein phosphatases in mammalian cells which plays an important role in regulating biological activities such as cellular mitosis and protein dephosphorylation.PP2A acts as a tumor suppressor and has been demonstrated to be genetically altered or functionally inactivated in a variety of solid cancers and leukemias,and its activity is inhibited,leading to subsequent proliferation of tumor cells.Clinical studies have shown that endogenous inhibitors such as SET,cancerous inhibitor of PP2A(CIP2A)and protein phosphatase methylesterase-1(PME-1)may reduce PP2A activity,which could be important indicators of tumor progression or recurrence.On the other hand,PP2A-activating drugs(e.g.FTY720)can restore the tumor-suppressing activity of PP2A by altering the structure of the inhibitor SET,thus effectively inhibiting tumor development.Therefore,PP2A and its inhibitors may serve as potential therapeutic targets in clinic.This article provides a comprehensive review on the mechanism of action of PP2A and its inhibitors in the pathogenesis of malignant tumor as well as their applications in oncotherapy,aiming to provide new directions for the treatment of malignant tumors.

关 键 词：蛋白磷酸酶2A 内源性抑制剂 肿瘤 蛋白磷酸酶2A癌症抑制剂 蛋白磷酸酶甲基酯酶-1 

分 类 号：R730.2[医药卫生—肿瘤]