ArticleBMC biology2021
The mitochondrially-localized nucleoside diphosphate kinase D (NME4) is a novel metastasis suppressor.
Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Iron-endoplasmic reticulum-extracellular matrix axis regulates cancer cell invasion.bioRxiv : the preprint server for biology · 2026Article
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Functional Diversity and Emerging Roles of Human NME/NDPK Group II Proteins.International journal of molecular sciences · 2026Review
- Cell Death Induced by Homoisoflavonoid Brazilin and Its Semisynthetic Derivatives on MDA-MB-231 and MCF7 Breast Cancer Cell Lines.ACS omega · 2026Article
- Upregulation ofTranslational andrology and urology · 2026Article
- Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Mitochondrial NME6 Influences Basic Cellular Processes in Tumor Cells In Vitro.International journal of molecular sciences · 2024Article
- Review
- Review
- Creatine kinase elevation in chronic hepatitis B patients with telbivudine therapy: influence of telbivudine plasma concentration and single nucleotide polymorphisms of TK2, RRM2B, and NME4.European journal of clinical pharmacology · 2024Observational
- PRUNE1 and NME/NDPK family proteins influence energy metabolism and signaling in cancer metastases.Cancer metastasis reviews · 2024Review
- Context-dependent roles for ubiquitous mitochondrial creatine kinase CKMT1 in breast cancer progression.Cell reports · 2024Article
- Metastasis suppressor genes in clinical practice: are they druggable?Cancer metastasis reviews · 2023Review
- Mechanisms of action of NME metastasis suppressors - a family affair.Cancer metastasis reviews · 2023Review
- Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial HPharmaceutical biology · 2023Review
- Fuzzy optimization for identifying antiviral targets for treating SARS-CoV-2 infection in the heart.BMC bioinformatics · 2023Article
- Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells.Biochemistry and biophysics reports · 2023Article
- Role of mitochondrial alterations in human cancer progression and cancer immunity.Journal of biomedical science · 2023Review
- Molecular and Pathological Analyses of IARS1-Deficient Mice: An IARS Disorder Model.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
29 authors at 12 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitochondrial nucleoside diphosphate kinase (NDPK-D, NME4, NM23-H4) is a multifunctional enzyme mainly localized in the intermembrane space, bound to the inner membrane.
resultsWe constructed loss-of-function mutants of NDPK-D, lacking either NDP kinase activity or membrane interaction and expressed mutants or wild-type protein in cancer cells. In a complementary approach, we performed depletion of NDPK-D by RNA interference. Both loss-of-function mutations and NDPK-D depletion promoted epithelial-mesenchymal transition and increased migratory and invasive potential. Immunocompromised mice developed more metastases when injected with cells expressing mutant NDPK-D as compared to wild-type. This metastatic reprogramming is a consequence of mitochondrial alterations, including fragmentation and loss of mitochondria, a metabolic switch from respiration to glycolysis, increased ROS generation, and further metabolic changes in mitochondria, all of which can trigger pro-metastatic protein expression and signaling cascades. In human cancer, NME4 expression is negatively associated with markers of epithelial-mesenchymal transition and tumor aggressiveness and a good prognosis factor for beneficial clinical outcome.
conclusionsThese data demonstrate NME4 as a novel metastasis suppressor gene, the first localizing to mitochondria, pointing to a role of mitochondria in metastatic dissemination.
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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 Socratic graph.