ArticleCells2020
Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Progress of Research on the Metabolic Regulation of Lactylation in Muscle Tissues and Its Disease Associations.Biomolecules · 2026Review
- Lactylation-driven gene signatures define breast cancer prognosis: a predictive model and insights into immune microenvironment dynamics.European journal of medical research · 2026Article
- Review
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- The new insights of lactate in various kidney diseases.Expert reviews in molecular medicine · 2025Review
- GPR55 senses lactate to sustain motility in prostate cancer cells.Molecular and cellular biochemistry · 2025Article
- Article
- The Role of Perirenal Adipose Tissue in Carcinogenesis-From Molecular Mechanism to Therapeutic Perspectives.Cancers · 2025Review
- Lactate modulates zygotic genome activation through H3K18 lactylation rather than H3K27 acetylation.Cellular and molecular life sciences : CMLS · 2024Article
- Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy.Cancer metastasis reviews · 2023Review
- Reprogramming of glucose metabolism via PFKFB4 is critical in FGF16-driven invasion of breast cancer cells.Bioscience reports · 2023Article
- A monocarboxylate transporter-dependent mechanism confers resistance to exercise-induced fatigue in a high-altitude hypoxic environment.Scientific reports · 2023Article
- Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction.Science advances · 2023Article
- New insights into fibrotic signaling in renal cell carcinoma.Frontiers in cell and developmental biology · 2023Review
- Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma.Frontiers in oncology · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets.International journal of molecular sciences · 2022Review
- Downregulation of mMolecular oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRenal cell carcinoma (RCC) displays a glycolytic phenotype (Warburg effect). Increased lactate production, impacting on tumor biology and microenvironment modulation, has been implicated in epigenetic mechanisms' regulation, leading to histone deacetylases inhibition. Thus, in-depth knowledge of lactate's impact on epigenome regulation of highly glycolytic tumors might allow for new therapeutic strategies. Herein, we investigated how extracellular lactate affected sirtuin 1 activity, a class III histone deacetylase (sirtuins, SIRTs) in RCC.
methodsIn vitro and in vivo interactions between lactate and SIRT1 in RCC were investigated in normal kidney and RCC cell lines. Finally, SIRT1 and N-cadherin immunoexpression was assessed in human RCC and normal renal tissues.
resultsLactate inhibited SIRT1 expression in normal kidney and RCC cells, increasing global H3 and H3K9 acetylation. Cells exposed to lactate showed increased cell migration and invasion entailing a mesenchymal phenotype. Treatment with a SIRT1 inhibitor, nicotinamide (NAM), paralleled lactate effects, promoting cell aggressiveness. In contrast, alpha-cyano-4-hydroxycinnamate (CHC), a lactate transporter inhibitor, reversed them by blocking lactate transport. In vivo (chick chorioallantoic membrane (CAM) assay), lactate and NAM exposure were associated with increased tumor size and blood vessel recruitment, whereas CHC displayed the opposite effect. Moreover, primary RCC revealed N-cadherin upregulation whereas SIRT1 expression levels were downregulated compared to normal tissues.
conclusionsIn RCC, lactate enhanced aggressiveness and modulated normal kidney cell phenotype, in part through downregulation of SIRT1, unveiling tumor metabolism as a promising therapeutic target.
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