ArticlePLoS biology2020
Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 121 citations in OpenAlex.
- Uric acid enhances tumor stemness in breast cancer cells by upregulating GMPS.Molecular medicine reports · 2026Article
- Multidimensional molecular mechanisms of drug resistance in breast cancer: Implications for clinical decision‑making and treatment strategies (Review).Oncology reports · 2026Review
- E3 ubiquitin-ligase Hakai regulates LRP4 stability and Wnt/β-catenin signalling in colorectal cancer cells.iScience · 2026Article
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- HHEX-PRKAR2B axis-mediated PKA activation drives glucose metabolism-dependent progression of pancreatic ductal adenocarcinoma.iScience · 2026Article
- Integrative network toxicology and experimental evidence reveal mechanisms underlying diethyl phthalate-induced initiation and progression of endometrial cancer.Scientific reports · 2026Article
- Downregulation of PRPS2 inhibits tumor growth of non-small cell lung cancer by suppressing PI3K/AKT signaling.Frontiers in medicine · 2026Article
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- Integrative mendelian randomization and multi-omics analysis reveal a gut microbiota-metabolite-CXCL10 axis in breast cancer.AMB Express · 2025Article
- METTL3 drives malignant progression in TP53-mutant prostate cancer.Molecular biology reports · 2025Article
- The Interventional Effects and Mechanisms of Lonidamine in Combination with Apigenin on Colorectal Cancer.Current issues in molecular biology · 2025Article
- Methylation aberrations and genomic instability synergistically drive the evolution of intrahepatic cholangiocarcinoma.Epigenomics · 2025Article
- PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights.Current issues in molecular biology · 2025Article
- Review
- PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells.Discover oncology · 2025Article
- A study on the microbiome within oropharyngeal cancer tissues.Discover oncology · 2025Article
- SNP's use as a potential chemotoxicity stratification tool in breast cancer: from bench to clinic.Functional & integrative genomics · 2025Review
- Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients' tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient's survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.