dCTP焦磷酸酶1调节肿瘤细胞核苷酸代谢及表型的研究进展

Research progress of dCTP pyrophosphatase 1regulating nucleotide metabolism and phenotype of tumor cells

三磷酸脱氧胞苷焦磷酸酶1(dCTP焦磷酸酶1,DCTPP1)是新发现的靶向三磷酸脱氧胞苷(dCTP)的焦磷酸酶,它不仅通过水解常规性和修饰性dCTP调节胞嘧啶代谢,而且参与其他嘧啶核苷酸的稳态调节。肿瘤细胞进程中,DCTPP1的高表达有利于稳定脱氧核苷三磷酸池(dNTP池)的平衡和基因组的甲基化水平,维持肿瘤细胞基因组稳定性。此外,DCTPP1通过不同的信号途径促进肿瘤细胞的增殖、转移等恶性表型,并与肿瘤耐药及临床不良预后相关。DCTPP1或将成为抗肿瘤药物研发的“明星”靶点。对其调节机制的深入研究有望为肿瘤核苷酸代谢类靶向抑制剂研发提供新策略。

Deoxycytidine triphosphate pyrophosphatase 1(dCTP pyrophosphatase 1,DCTPP1)is a newly discovered pyrophosphatase targeting deoxycytidine triphosphate(dCTP).It regulates cytosine metabolism by not only hydrolyzing conventional and modified dCTP,but also participating in the steady-state regulation of other pyrimidine nucleotides.In the process of tumor cells,the high expression of DCTPP1 is facilitate to stabilize the balance of deoxynucleoside triphosphate pool(dNTP pool),methylation of the genome,and maintainance of stability of the tumor cell genome.Besides,DCTPP1 promotes malignant phenotypes such as tumor cell proliferation and metastasis through different signal pathways,and it is related to tumor drug resistance and poor clinical prognosis.DCTPP1 may become a“star”target for the development of anti-tumor drugs.In-depth research on its regulatory mechanism is expected to provide a new strategy for the development of targeted inhibitors of tumor nucleotide metabolism.