国际神经病学神经外科学杂志2025，Vol.52Issue(4)：70-78,9.DOI:10.16636/j.cnki.jinn.1673-2642.2025.04.011
磷酸甘油酸激酶1在颅内肿瘤中的作用研究进展
Research advances in the role of phosphoglycerate kinase 1 in intracranial tumors
摘要
Abstract
Phosphoglycerate kinase 1(PGK1)is a key enzyme in the glycolytic pathway that catalyzes the first ATP-generating step,and it plays a core role in intracranial tumors,especially gliomas,by driving metabolic reprogramming.PGK1 overexpression significantly enhances glycolytic activity(known as the Warburg effect)and inhibit mitochondrial oxidative phosphorylation,thereby meeting the demands for energy and biosynthetic precursors during rapid tumor proliferation.Beyond its canonical metabolic functions,PGK1 exhibits the non-canonical mechanisms of acting as a protein kinase to activate itself and promote the progression of malignant tumor through autophosphorylation(e.g.,at the Tyr324 locus).Studies have shown that PGK1 can be co-localized with β-catenin in glioma cells and promote the invasion and migration of tumor cells by enhancing the Wnt/β-catenin signaling pathway,and its translocation to the subcellular compartments such as the nucleus may also regulate gene transcription and accelerate tumor metastasis.PGK1 dysregulation is a critical factor in therapeutic resistance of intracranial tumors:on the one hand,the upregulated expression of PGK1 enhances autophagy and help tumor cells clear chemotherapy-induced damage;on the other hand,PGK1 disturbs the balance between glycolysis and the tricarboxylic acid cycle through dynamic O-GlcNAc glycosylation,thereby leading to microenvironment acidification and lactate accumulation and reducing drug delivery efficiency;furthermore,PGK1 may indirectly participate in DNA repair by influencing nucleotide synthesis,thereby reducing radiosensitivity.These mechanisms collectively enhance tumor tolerance to radiotherapy and chemotherapy.As an important prognostic biomarker,PGK1 is highly expressed in astrocytomas and other intracranial tumors,which is correlated with the poor survival rates of patients.Combined detection of specific post-translational modifications of PGK1,such as autophosphorylation(pY324-PGK1)and arginine methylation(meR206-PGK1),can further improve the accuracy of prognostic assessment.In the realm of targeted therapy,PGK1 presents multifaceted intervention potential:small-molecule inhibitors effectively block ATP generation by targeting its kinase domain and inhibit tumor growth in preclinical models;combined targeting of upstream regulators(e.g.,inhibiting PRMT1-mediated methylation or ERK-mediated phosphorylation)offers indirect strategies to disrupt its function;in addition,targeting differentially expressed PGK1 within tumor-associated immune cells,such as tumor-associated macrophages,can reshape the immunosuppressive microenvironment and provide new strategies for combined immunotherapy.This article reviews the research advances in the mechanisms of action of PGK1 in the pathogenesis and progression of intracranial tumors,in order to provide new insights for exploring the treatment of intracranial tumors.关键词
磷酸甘油酸激酶1/颅内肿瘤/代谢重编程/瓦尔堡效应/治疗抵抗/预后标志物/翻译后修饰/靶向治疗Key words
phosphoglycerate kinase 1/intracranial tumors/metabolic reprogramming/Warburg effect/therapeutic resistance/prognostic biomarker/post-translational modifications/targeted therapy分类
医药卫生引用本文复制引用
胡德豫,孙岩,贺峭伟,张洪涛..磷酸甘油酸激酶1在颅内肿瘤中的作用研究进展[J].国际神经病学神经外科学杂志,2025,52(4):70-78,9.基金项目
2021年度山东省医学会临床科研资金-齐鲁专项(YXH2022ZX02183). （YXH2022ZX02183）
