UPP1, short for Uridine phosphorylase 1, is a dimeric enzyme crucial for pyrimidine salvage and uridine homeostasis. It catalyzes the reversible phosphorylation of uridine to uracil and ribose-1-phosphate [2,3]. UPP1-related pathways include the salvage of ribose from uridine, which can support glycolysis in nutrient-limited conditions, entering downstream of highly regulated steps of glucose transport and upper glycolysis [6].

In various cancers, UPP1 has been shown to play oncogenic roles. In lung adenocarcinoma (LUAD), UPP1high tumor cells are associated with an immunosuppressive tumor microenvironment. UPP1 upregulation leads to increased release of immunosuppressive cytokines like TGF-β1 and elevation of PD-L1 expression via the PI3K/AKT/mTOR pathway, suppressing CD8+ T cells [1]. UPP1 also promotes LUAD progression by driving glycolytic metabolism, and is epigenetically regulated through histone acetylation [2]. In bladder cancer, UPP1 promotes cell proliferation, migration, invasion, and gemcitabine resistance by activating the AKT signaling pathway [3]. In gliomas, high levels of UPP1 are linked to poor survival, and it promotes tumor cell proliferation, invasion, and immune evasion [5]. In pancreatic ductal adenocarcinoma, UPP1 is regulated by KRAS-MAPK signalling, and its deletion restricts tumor growth in immunocompetent mouse models as it liberates uridine-derived ribose to support cancer cell survival and proliferation in glucose-restricted conditions [4].

In conclusion, UPP1 is a key enzyme in pyrimidine metabolism and is significantly involved in the progression of multiple cancers, including LUAD, bladder cancer, gliomas, and pancreatic cancer. Functional studies, especially those using gene knockout or conditional knockout mouse models, have revealed its role in promoting tumorigenesis, immunosuppression, and metabolic reprogramming in these disease conditions, highlighting its potential as a therapeutic target [1,2,3,4,5].