Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Islamic Republic of Iran.
Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Islamic Republic of Iran.
Med Oncol. 2023 Jun 26;40(8):213. doi: 10.1007/s12032-023-02086-7.
Cancer cells require continuous synthesis of nucleotides for their uncontrolled proliferation. Deoxy thymidylate kinase (DTYMK) belongs to the thymidylate kinase family and is concerned with pyrimidine metabolism. DTYMK catalyzes the ATP-based conversion of deoxy-TMP to deoxy-TDP in both de novo and salvage pathways. Different studies demonstrated that DTYMK was increased in various types of cancers such as hepatocellular carcinoma, colon cancer, lung cancer, etc. Increased level of DTYMK was associated with poorer survival and prognosis, stage, grade and size of tumor, cell proliferation, colony formation, enhanced sensitivity to chemotherapy drugs, migration. Some studies were showed that knockdown of DTYMK reduced the signaling pathway of PI3K/AKT and downregulated expression of CART, MAPKAPK2, AKT1 and NRF1. Moreover, some microRNAs could suppress DTYMK expressions. On the other hand based on the TIMER database, the infiltration of macrophages, dendritic cells, neutrophils, B cells, CD4+ T cell and CD8+ T cell is affected by DTYMK. In the present review, we describe the genomic location, protein structure and isoforms of DTYMK and focus on its role in cancer development.
癌细胞的无节制增殖需要不断合成核苷酸。脱氧胸苷酸激酶 (DTYMK) 属于胸苷酸激酶家族，与嘧啶代谢有关。DTYMK 在从头合成途径和补救途径中均催化 ATP 依赖的脱氧-TMP 向脱氧-TDP 的转化。不同的研究表明，DTYMK 在多种类型的癌症中增加，如肝癌、结肠癌、肺癌等。DTYMK 水平的升高与生存率和预后不良、肿瘤的分期、分级和大小、细胞增殖、集落形成、对化疗药物的敏感性增加、迁移等有关。一些研究表明，敲低 DTYMK 可降低 PI3K/AKT 信号通路的活性，并下调 CART、MAPKAPK2、AKT1 和 NRF1 的表达。此外，一些 microRNAs 可以抑制 DTYMK 的表达。另一方面，基于 TIMER 数据库，巨噬细胞、树突状细胞、嗜中性粒细胞、B 细胞、CD4+T 细胞和 CD8+T 细胞的浸润受到 DTYMK 的影响。在本综述中，我们描述了 DTYMK 的基因组位置、蛋白质结构和同工型，并重点介绍了其在癌症发展中的作用。
