The evolving landscape of involvement of DTYMK enzymes in cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Cancer cells exhibit uncontrolled proliferation, necessitating continuous nucleotide synthesis.
• Deoxy thymidylate kinase (DTYMK), crucial for pyrimidine metabolism, catalyzes deoxy-TMP to deoxy-TDP conversion.
• DTYMK is upregulated in various cancers, including hepatocellular carcinoma, colon, and lung cancer.

Purpose of the Study:

• To review the genomic location, protein structure, and isoforms of DTYMK.
• To elucidate the role of DTYMK in cancer development and progression.
• To explore DTYMK's impact on cancer cell signaling, proliferation, and immune cell infiltration.

Main Methods:

• Literature review of studies on DTYMK in cancer.
• Analysis of DTYMK's enzymatic activity in nucleotide metabolism.
• Examination of DTYMK expression levels in different cancer types.
• Investigation of DTYMK's association with clinical parameters and patient prognosis.
• Review of DTYMK's influence on cellular pathways (e.g., PI3K/AKT) and immune cell infiltration (via TIMER database).

Main Results:

• Elevated DTYMK levels correlate with poorer survival, advanced tumor stage, grade, and size.
• DTYMK influences cell proliferation, colony formation, migration, and chemotherapy sensitivity.
• Knockdown of DTYMK downregulates PI3K/AKT signaling and specific genes (CART, MAPKAPK2, AKT1, NRF1).
• MicroRNAs can suppress DTYMK expression.
• DTYMK affects the infiltration of various immune cells, including macrophages, dendritic cells, neutrophils, B cells, CD4+ T cells, and CD8+ T cells.

Conclusions:

• DTYMK is a significant factor in cancer development and progression across multiple tumor types.
• DTYMK's role extends to influencing cancer cell behavior and the tumor microenvironment's immune landscape.
• Understanding DTYMK's functions provides insights into potential therapeutic targets for cancer treatment.