ArticleBreast cancer research : BCR2024
The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth.
Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- Pyrroline-5-carboxylate reductase 1 interacts with Nudix hydrolase 5 to drive bladder cancer malignant progression via activation of the APOE/JAK2/STAT3 signalling axis.Clinical and translational medicine · 2026Article
- Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response.Nature communications · 2026Article
- The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.BMC medicine · 2026Review
- Uridine-sensitized screening identifies demethoxy-coenzyme Q and NUDT5 as regulators of nucleotide synthesis.Nature metabolism · 2025Article
- Quercetin and Its Structural Analogs as NUDT5 Inhibitors: A Preliminary In Silico Study.International journal of molecular sciences · 2025Article
- Targeting Mitochondrial Quality Control for the Treatment of Triple-Negative Breast Cancer: From Molecular Mechanisms to Precision Therapy.Biomolecules · 2025Review
- Targeting Nudix Hydrolase 5 with Bioactive Flavonoids: Molecular Dynamics and Docking Studies for Breast Cancer Therapy.Cell biochemistry and biophysics · 2025Article
- Identification of potential NUDT5 inhibitors from marine bacterial natural compounds via molecular dynamics and free energy landscape analysis.Molecular diversity · 2025Article
- Assessment of NUDT5 in Endometrial Carcinoma: Functional Insights, Prognostic and Therapeutic Implications.Biomedicines · 2025Article
- Intratumour oxidative hotspots provide a niche for cancer cell dissemination.Nature cell biology · 2025Article
- The multifaceted regulatory roles of Nudix hydrolases in cancer and their therapeutic potential.Frontiers in oncology · 2025Review
- Repurposing fluvoxamine as an inhibitor for NUDT5 in breast cancer cell: an in silico and in vitro study.In silico pharmacology · 2025Article
- Correction: The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth.Breast cancer research : BCR · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target for TNBC.
methodsThe mRNA expression levels of NUDT5 in breast cancers were investigated using TCGA and METABRIC (Curtis) datasets. NUDT5 ablation was achieved through siRNA targeting and NUDT5 inhibition with the small molecule inhibitor TH5427. Xenograft TNBC animal models were employed to assess the effect of NUDT5 inhibition on in vivo tumor growth. Proliferation, death, and DNA replication assays were conducted to investigate the cellular biological effects of NUDT5 loss or inhibition. The accumulation of 8-oxo-guanine (8-oxoG) and the induction of γH
resultsIn this study, we demonstrated the significant role of an overexpressed phosphatase, NUDT5, in regulating oxidative DNA damage in TNBCs. Our findings indicate that loss of NUDT5 results in suppressed growth of TNBC both in vitro and in vivo. This growth inhibition is not attributed to cell death, but rather to the suppression of proliferation. The loss or inhibition of NUDT5 led to an increase in the oxidative DNA lesion 8-oxoG, and triggered the DNA damage response in the nucleus. The interference with DNA replication ultimately inhibited proliferation.
conclusionsNUDT5 plays a crucial role in preventing oxidative DNA damage in TNBC cells. The loss or inhibition of NUDT5 significantly suppresses the growth of TNBCs. These biological and mechanistic studies provide the groundwork for future research and the potential development of NUDT5 inhibitors as a promising therapeutic approach for TNBC patients.
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