ArticleInternational journal of biological sciences2022
A Positive Feedback Loop between Inactive VHL-Triggered Histone Lactylation and PDGFRβ Signaling Drives Clear Cell Renal Cell Carcinoma Progression.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
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Who cites it
176 citing papers in PubMed, 219 citations in OpenAlex.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- H4K12 Lactylation Impairs Dopaminergic Neuron Energy Metabolism via the HIF-1α/NDUFS1 Pathway in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BRD9 recognizes lactate-induced H3K18 lactylation to drive oncogenic chromatin remodeling in hepatocellular carcinoma.Cell death and differentiation · 2026Article
- Research progress of lactylation modification in tumors (Review).Experimental and therapeutic medicine · 2026Review
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- Article
- UPR-CEBPB-MIF Signaling Links to Macrophage Polarization and an Immunosuppressive Tumor Microenvironment in Clear Cell Renal Cell Carcinoma.Annals of surgical oncology · 2026Article
- AARS1-catalyzed H4K12 lactylation promotes HCC resistance to targeted therapy by activating RAPGEF3-RAP1 signaling.Cell death & disease · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Hypoxia-induced PLOD3 activates the NEDD4/GOT2 axis to exacerbate renal cell carcinoma progression.Cell death & disease · 2026Article
- Histone delactylation shapes epigenetic landscapes and therapeutic stratification in hepatocellular carcinoma.iLIVER · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanistic Insights Into Recurrent Implantation Failure: The Lactate-H3K18la-SLC7A11 Axis Explored via Endometrial Organoid and Blastoid-Endometrial Cell Implantation Models.Cell proliferation · 2026Article
- Mechanisms and therapeutic implications of metabolic heterogeneity and histone lactylation in clear cell renal cell carcinoma.Discover oncology · 2026Review
- Review
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Identification and Screening of Lactate-Related Genes as Molecular Markers for Early Diagnosis of Steroid-Induced Osteonecrosis of the Femoral Head.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeting KIF20A blocks lactylation modification to suppress immune escape in hepatocellular carcinoma.iScience · 2026Article
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
116 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inactive von Hippel-Lindau (VHL) is linked to metabolic reprogramming and plays pivotal roles in the pathogenesis of clear cell renal cell carcinoma (ccRCC). Here, we identify a previously unknown oncogenic role for inactive VHL in actively triggering histone lactylation to promote ccRCC progression. In patients with ccRCC, inactive VHL positively correlates with the presence of histone lactylation, and high levels of histone lactylation indicates poor patient prognosis. Inactive VHL-triggered histone lactylation contributes to ccRCC progression by activating the transcription of platelet-derived growth factor receptor β (PDGFRβ). In turn, PDGFRβ signaling is shown to stimulate histone lactylation, thereby forming an oncogenic positive feedback loop in ccRCC. Target correction of aberrant histone lactylation represses the growth and metastasis of ccRCC in vivo. More importantly, the combined inhibition of histone lactylation and PDGFRβ significantly reinforces the therapeutic efficacy. This work underscores the importance of histone lactylation in facilitating ccRCC progression and suggests targeting the positive feedback loop between histone lactylation and PDGFRβ signaling might provide a promising therapeutic strategy for ccRCC patients.
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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.