Uridine Phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes

ABSTRACT: Understanding mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches to reduce metastasis. Here we identify uracil as a metastasis-associated metabolite in genetically engineered mouse models of cancer and in patients with metastatic breast cancer. Uracil is generated by the enzyme uridine phosphorylase-1 (UPP1), and we find that neutrophils are a significant source of UPP1 in metastatic cancer. Mammary tumours increase expression of adhesion molecules on the neutrophil surface, in a UPP1-dependent manner, leading to decreased neutrophil motility in the pre-metastatic lung. UPP1-expressing neutrophils suppress T cell proliferation, and the UPP1 product uracil increases fibronectin deposition in the extracellular microenvironment. Knockout

SUBMITTER: Declan Whyte 

PROVIDER: S-SCDT-10_1038-S44319-025-00520-7 | biostudies-other |

REPOSITORIES: biostudies-other