ArticleEMBO molecular medicine2019
The mitochondrial deoxyguanosine kinase is required for cancer cell stemness in lung adenocarcinoma.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Nucleotide salvage, genome instability, and potential therapeutic applications.Nucleic acids research · 2026Review
- Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma.Nature communications · 2025Article
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- Metabolic reprogramming driven by Ant2 deficiency augments T Cell function and anti-tumor immunity in mice.Nature communications · 2025Article
- Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.Current cancer drug targets · 2025Article
- Oxidative phosphorylation related gene COA6 is a novel indicator for the prognosis and immune response in lung adenocarcinoma.Scientific reports · 2024Article
- M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression via miR-520g-3p/SMIM22/GALE axis.NPJ precision oncology · 2024Article
- Proteomic Profiling of Hindlimb Skeletal Muscle Disuse in a Murine Model of Sepsis.Critical care explorations · 2024Article
- Mitochondrial deoxyguanosine kinase is required for female fertility in mice.Acta biochimica et biophysica Sinica · 2024Article
- Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis.Cancers · 2024Article
- Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant.Signal transduction and targeted therapy · 2023Article
- Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma.Frontiers in oncology · 2023Article
- Review
- Long non-coding RNA DARS-AS1 promotes tumor progression by directly suppressing PACT-mediated cellular stress.Communications biology · 2022Article
- Mitochondrial Calcium Uniporter Drives Metastasis and Confers a Targetable Cystine Dependency in Pancreatic Cancer.Cancer research · 2022Article
- Entecavir competitively inhibits deoxyguanosine and deoxyadenosine phosphorylation in isolated mitochondria and the perfused rat heart.The Journal of biological chemistry · 2022Article
- Establishment and characterization of a novel highly malignant lung cancer cell line ZX2021H derived from a metastatic lymph node lesion.Thoracic cancer · 2022Article
- Fascin promotes lung cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression.Cancer letters · 2021Article
- The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance.Cell death & disease · 2021Review
- Potential biomarkers and targets of mitochondrial dynamics.Clinical and translational medicine · 2021Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK KO lung cancer cells using NDI1 was able to prevent AMPK-mediated phosphorylation of YAP and to rescue CSC stemness. Genetic targeting of DGUOK using doxycycline-inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC-mediated therapy resistance and metastatic recurrence.
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Registered trials
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.