ArticleInternational journal of molecular sciences2021
Lactate Suppresses Retroviral Transduction in Cervical Epithelial Cells through DNA-PKcs Modulation.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Harnessing the Vaginal Microbiome: A New Frontier in the Prevention of Sexually Transmitted Infections.Expert reviews in molecular medicine · 2026Review
- Review
- The microbiota-host metabolic axis in cervical cancer: from homeostatic disruption to mechanisms of therapy resistance.Frontiers in cellular and infection microbiology · 2026Review
- Lactic acid metabolism: gynecological cancer's Achilles' heel.Discover oncology · 2025Review
- The role of MCT1 in tumor progression and targeted therapy: a comprehensive review.Frontiers in immunology · 2025Review
- SARS-CoV-2-related peptides induce endothelial-to-mesenchymal transition in endothelial capillary cells derived from different body districts: focus on membrane (M) protein.Cell and tissue research · 2024Article
- Endothelial-to-Mesenchymal Transition: Potential Target of Doxorubicin-Induced Cardiotoxicity.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Review
- Interactions between microbiota and cervical epithelial, immune, and mucus barrier.Frontiers in cellular and infection microbiology · 2023Review
- Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers.Cancers · 2022Review
- Lactate drives cellular DNA repair capacity: Role of lactate and related short-chain fatty acids in cervical cancer chemoresistance and viral infection.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, we have shown the molecular basis for lactate sensing by cervical epithelial cells resulting in enhanced DNA repair processes through DNA-PKcs regulation. Interestingly, DNA-PKcs is indispensable for proper retroviral DNA integration in the cell host genome. According to recent findings, the mucosal epithelium can be efficiently transduced by retroviruses and play a pivotal role in regulating viral release by cervical epithelial cells. This study examined the effects of lactate on lentiviral transduction in cervical cancer cells (HeLa, CaSki, and C33A) and model glioma cell lines (DNA-PKcs proficient and deficient). Our study showed that L- and D-lactate enhanced DNA-PKcs presence in nuclear compartments by between 38 and 63%, which corresponded with decreased lentiviral transduction rates by between 15 and 36%. Changes in DNA-PKcs expression or its inhibition with NU7441 also greatly affected lentiviral transduction efficacy. The stimulation of cells with either HCA1 agonist 3,5-DHBA or HDAC inhibitor sodium butyrate mimicked, in part, the effects of L-lactate. The inhibition of lactate flux by BAY-8002 enhanced DNA-PKcs nuclear localization which translated into diminished lentiviral transduction efficacy. Our study suggests that L- and D-lactate present in the uterine cervix may play a role in the mitigation of viral integration in cervical epithelium and, thus, restrict the viral oncogenic and/or cytopathic potential.
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