UPP1, also known as uridine phosphorylase 1, is a dimeric enzyme that plays a crucial role in pyrimidine salvage and uridine homeostasis [2]. It catalyzes the reversible phosphorylation of uridine to uracil and ribose-1-phosphate, and its activity is involved in multiple metabolic pathways, including those related to energy production and nucleotide synthesis [3].

In various cancers, UPP1 has been shown to promote tumor progression. In lung adenocarcinoma (LUAD), UPP1-high tumor cells are associated with an immunosuppressive microenvironment. UPP1 upregulation leads to increased release of immunosuppressive cytokines like TGF-β1 and elevates PD-L1 expression via the PI3K/AKT/mTOR pathway, suppressing CD8+ T cells [1]. Additionally, UPP1 drives glycolytic metabolism in LUAD, and its expression is subject to epigenetic regulation 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 liberates uridine-derived ribose to fuel central carbon metabolism in glucose-restricted conditions [4].

In conclusion, UPP1 is a key enzyme in pyrimidine metabolism with significant implications in cancer progression. Studies, although not specifically highlighting KO/CKO mouse models in the provided references, suggest its role in promoting tumorigenesis and immunosuppression in multiple cancer types, making it a potential therapeutic target for these diseases.