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The evolving landscape of involvement of DTYMK enzymes in cancer

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Abstract

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.

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Authors and Affiliations

  1. Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Islamic Republic of Iran

    Nadia Heydari, Mahsa Mahdizadeh & Seyyed Mehdi Jafari

  2. Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Islamic Republic of Iran

    Nadia Heydari, Mahsa Mahdizadeh & Seyyed Mehdi Jafari

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  1. Nadia Heydari
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Heydari, N., Mahdizadeh, M. & Jafari, S.M. The evolving landscape of involvement of DTYMK enzymes in cancer. Med Oncol 40, 213 (2023). https://doi.org/10.1007/s12032-023-02086-7

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