肿瘤细胞需要进行代谢重编程以实现快速发展和进展，癌细胞的其中一个代谢特点是过度合成和利用核苷酸。异常增加的核苷酸及其代谢产物不仅可以直接加速肿瘤细胞的进展，还可以通过旁分泌的方式间接作用于肿瘤微环境中的基质细胞以调节肿瘤进展。嘌呤核苷酸主要通过肿瘤细胞的新生核苷酸合成产生；因此，干预其合成已成为一种有希望的抗肿瘤治疗策略。新生嘌呤合成是由六个酶催化的十步反应，用于合成肿瘤细胞中的肌苷5-磷酸（IMP），并进一步合成AMP和GMP。磷酸核糖氨基咪唑羧化酶/磷酸核糖氨基咪唑琥珀酰氨转化酶（PAICS）是一个双功能酶，催化新生嘌呤合成。各种肿瘤中PAICS的异常高表达与不良预后有关。证据表明，PAICS及其催化产物N-琥珀酰胺-5-氨基咪唑核苷酸（SAICAR）通过调节丙酮酸激酶M2（PKM2），细胞外信号调节激酶1和2（ERK1/2），黏附斑激酶（FAK）等信号通路，可以抑制肿瘤细胞凋亡，促进生长、上皮间质转化（EMT）、侵袭和转移。本综述总结了PAICS在癌症发展中的结构、生物学功能和分子机制，并讨论了其作为肿瘤治疗靶点的潜力。版权所有©2023 Elsevier公司发表。

Tumor cells are required to undergo metabolic reprogramming for rapid development and progression, and one of the metabolic characteristics of cancer cells is the excessive synthesis and utilization of nucleotides. Abnormally increased nucleotides and their metabolites not only directly accelerate tumor cell progression but also indirectly act on stromal cells in the tumor microenvironment (TME) via a paracrine manner to regulate tumor progression. Purine nucleotides are mainly produced via de novo nucleotide synthesis in tumor cells; therefore, intervening in their synthesis has emerged as a promising strategy in anti-tumor therapy. De novo purine synthesis is a 10-step reaction catalyzed by six enzymes to synthesize inosine 5-monophosphate (IMP) and subsequently synthesize AMP and GMP. Phosphoribosylaminoimidazole carboxylase/phosphori-bosylaminoimidazole succinocarboxamide synthetase (PAICS) is a bifunctional enzyme that catalyzes de novo purine synthesis. Aberrantly elevated PAICS expression in various tumors is associated with poor prognosis. Evidence suggests that PAICS and its catalytic product, N-succinylcarboxamide-5-aminoimidazole ribonucleotide (SAICAR), could inhibit tumor cell apoptosis and promote the growth, epithelial-mesenchymal transition (EMT), invasion, and metastasis by regulating signaling pathways such as pyruvate kinase M2 (PKM2), extracellular signal-related kinases 1 and 2 (ERK1/2), focal adhesion kinase (FAK) and so on. This review summarizes the structure, biological functions and the molecular mechanisms of PAICS in cancer development and discusses its potential to be a target for tumor therapy.Copyright © 2023. Published by Elsevier Inc.