Enhanced
nucleoside metabolism is one of the hallmarks of
cancer.
Uridine-cytidine kinase 2 (UCK2) is a rate-limiting
enzyme of the
pyrimidine salvage synthesis pathway to phosphorylate
uridine and
cytidine to
uridine monophosphate (
UMP) and
cytidine monophosphate (
CMP), respectively. Recent studies have shown that UCK2 is overexpressed in many types of solid and hematopoietic
cancers, closely associates with poor prognosis, and promotes cell proliferation and migration in
lung cancer and HCCs. Although UCK2 is thought to catalyze sufficient
nucleotide building blocks to support the rapid proliferation of
tumor cells, we and other groups have recently demonstrated that UCK2 may play a
tumor-promoting role in a catalytic independent manner by activating oncogenic signaling pathways, such as STAT3 and EGFR-AKT. By harnessing the catalytic activity of UCK2, several cytotoxic ribonucleoside analogs, such as
TAS-106 and
RX-3117, have been developed for UCK2-mediated
cancer chemotherapy. Moreover, we have demonstrated that the concurrent targeting of the catalytic dependent and independent features of UCK2 could synergistically inhibit
tumor growth. These findings suggest that UCK2 may serve as a potential therapeutic target for
cancer treatment. In this mini-review, we introduced the genomic localization and
protein structure of UCK2, described the role of UCK2 in
tumor development, discussed the application of UCK2 in anti-
tumor treatment, and proposed concurrent targeting of the catalytic and non-catalytic roles of UCK2 as a potential therapeutic strategy for
cancer treatment.