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Uric acid enhances tumor stemness in breast cancer cells by upregulating GMPS.

Created on 14 Aug 2026

Authors

Zhiying Wang, Mingzhang Huang, Yuanqi Zhang, Siqi Huang, Wei Lei, Xiaorong Shui

Published in

Molecular medicine reports. Volume 34. Issue 4. Epub Aug 14, 2026.

Abstract

Metabolic reprogramming is closely associated with the development and progression of cancer and is considered an emerging hallmark of cancer. To meet the bioenergetic and biosynthetic demands, tumor cells tend to initiate the metabolic reprogramming process, creating a tumor microenvironment that is adaptable for cancer cell growth and further promote oncogenic signaling, cell proliferation and metastasis. As a final byproduct of purine metabolism, the uric acid (UA) concentration rises in the quickly growing tumor microenvironment. However, whether elevated UA affects the development and prognosis of patients with tumors has not been demonstrated. In the present study, Cell Counting Kit‑8 and scratch healing test were used to investigate the effects of UA on the proliferation and migration of breast cancer cells. The effects of UA on nucleotide de novo synthesis genes in breast cells were validated using quantitative PCR (qPCR) and western blotting (WB). The activation of stemness in breast cancer cells by UA was validated using colony formation assays, ELISA, qPCR and WB. Finally, clinical data and The Cancer Genome Atlas database were analyzed to examine the expression of de novo nucleotide synthesis genes in cancerous and adjacent tissues, as well as in different types of breast cancer tissues. The present study investigated the potential effect of UA on the function of breast cancer; it also determined how UA affected the genes involved in nucleotide de novo synthesis, as well as how it contributes to tumor stemness. It was discovered that UA could enhance tumor stemness in breast cancer cells through the upregulation of guanosine 5'‑monophosphate synthase (GMPS). It was notable that GMPS expression in patients with breast cancer may be strongly associated with the course of the disease and the prognosis of patients. In conclusion, the present study demonstrated that elevated UA upregulates GMPS and stimulates the migration and proliferation of breast cancer cells through the cyclic guanosine monophosphate/protein kinase G/mitogen‑activated protein kinase pathway axis.

PMID:
42596824
Bibliographic data and abstract were imported from PubMed on 14 Aug 2026.

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