ArticleJournal of hematology & oncology2019
Adenylate kinase 4 modulates oxidative stress and stabilizes HIF-1α to drive lung adenocarcinoma metastasis.
Article in Journal of hematology & oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.International journal of molecular sciences · 2026Review
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- Mitochondrial AK3 inhibits nuclear β-catenin localization and its activation through enhancing mitochondrial activity.Cell death & disease · 2026Article
- AK5 suppresses breast cancer progression and modulates anti-PD-L1 efficacy via the miR-182-5p/PD-L1 axis.iScience · 2026Article
- Adenylate kinase 4 promotes radioresistance by suppressing radiation-induced ferroptosis through metabolic regulation in glioblastoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Clinical and Molecular Differences of Hypertensive Disorders During Pregnancy.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Multiomics Analysis of Nucleotide Metabolism Highlights the Important Role of Adenylate Kinase 4 in Pancreatic Cancer.Human mutation · 2026Article
- The impact of hypoxia on the cellular phenotype and proteome of KGN cells.Reproduction & fertility · 2025Article
- Circ-06958 Is Involved in Meat Quality by Regulating Cell Proliferation Through miR-31-5p/AK4 Axis in Pigs.Cells · 2025Article
- AK4 promotes nasopharyngeal carcinoma metastasis and chemoresistance by activating NLRP3 inflammatory complex.Cell death & disease · 2025Article
- Identification of AK4 and RHOC as potential oncogenes addicted by adult T cell leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Withaferin-A inhibits colorectal cancer growth and metastasis by targeting the HSP90/HIF-1α/EMT axis.Archives of medical science : AMS · 2025Article
- Unraveling the alterations and biomarkers in the tumor microenvironment in lung adenocarcinoma metastases and their indications for therapeutic response and prognosis.Therapeutic advances in medical oncology · 2025Review
- Kinome-wide CRISPR-Cas9 screens revealedBiochemistry and biophysics reports · 2024Article
- Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases.Current issues in molecular biology · 2024Review
- Construction of a novel lipid drop-mitochondria-associated genetic profile for predicting the survival and prognosis of lung adenocarcinoma.Discover oncology · 2024Article
- Pan-cell death-related signature reveals tumor immune microenvironment and optimizes personalized therapy alternations in lung adenocarcinoma.Scientific reports · 2024Article
- MicroRNA-124 conducts neuroprotective effect via inhibiting AK4/ATF3 after subarachnoid hemorrhage.Experimental brain research · 2024Article
- Secreted HLA-Fc fusion profiles immunopeptidome in hypoxic PDAC and cellular senescence.PNAS nexus · 2023Article
- A key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.Epigenetics · 2023Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdenylate kinase 4 (AK4) has been identified as a biomarker of metastasis in lung cancer. However, the impacts of AK4 on metabolic genes and its translational value for drug repositioning remain unclear.
methodsIngenuity upstream analyses were used to identify potential transcription factors that regulate the AK4 metabolic gene signature. The expression of AK4 and its upstream regulators in lung cancer patients was examined via immunohistochemistry. Pharmacological and gene knockdown/overexpression approaches were used to investigate the interplay between AK4 and its upstream regulators during epithelial-to-mesenchymal transition (EMT). Drug candidates that reversed AK4-induced gene expression were identified by querying a connectivity map. Orthotopic xenograft mouse models were established to evaluate the therapeutic efficacy of drug candidates for metastatic lung cancer.
resultsWe found that HIF-1α is activated in the AK4 metabolic gene signature. IHC analysis confirmed this positive correlation, and the combination of both predicts worse survival in lung cancer patients. Overexpression of AK4 exaggerates HIF-1α protein expression by increasing intracellular ROS levels and subsequently induces EMT under hypoxia. Attenuation of ROS production with N-acetylcysteine abolishes AK4-induced invasion potential under hypoxia. Pharmacogenomics analysis of the AK4 gene signature revealed that withaferin-A could suppress the AK4-HIF-1α signaling axis and serve as a potent anti-metastatic agent in lung cancer.
conclusionsOverexpression of AK4 promotes lung cancer metastasis by enhancing HIF-1α stability and EMT under hypoxia. Reversing the AK4 gene signature with withaferin-A may serve as a novel therapeutic strategy to treat metastatic lung 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.