ArticleAngiogenesis2015
KSHV induces aerobic glycolysis and angiogenesis through HIF-1-dependent upregulation of pyruvate kinase 2 in Kaposi's sarcoma.
Article in Angiogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 100 citations in OpenAlex.
- KSHV vIRF3-PKM2 interaction induces SMAD5 acetylation, promoting Kaposi's sarcoma progression.Experimental & molecular medicine · 2026Article
- Review
- KSHV and cancer: understanding the oncogenic machinery for next-generation diagnostic tools and therapies.Archives of microbiology · 2026Review
- Promising Role of PKM2 in the Diagnosis and Prognosis of Ovarian Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- Conformational Dynamics of PKM2 Regulate Hypoxia-Induced Pathological Retinal Angiogenesis.Investigative ophthalmology & visual science · 2025Article
- Pyruvate kinase M2 modulates Japanese encephalitis virus replication in neuronal cells.The Journal of general virology · 2025Article
- PKM2 regulates angiogenic activation via ANGPT2 in endothelial cells.Scientific reports · 2025Article
- Oncogenic Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus on Cell Metabolism and Cell Transformation.Journal of medical virology · 2025Review
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.Frontiers in cell and developmental biology · 2025Review
- Understanding Metabolic Pathway Rewiring by Oncogenic Gamma Herpesvirus.Journal of microbiology and biotechnology · 2024Review
- Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis.Journal of nanobiotechnology · 2024Article
- PKM2 induces mitophagy through the AMPK-mTOR pathway promoting CSFV proliferation.Journal of virology · 2024Article
- Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus.Nature communications · 2024Article
- Review
- Sirtuin 1 activator alleviated lethal inflammatory injuryFrontiers in pharmacology · 2023Article
- Importance of lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs) in cancer cells.Health science reports · 2023Article
- Contribution of carbohydrate-related metabolism in Herpesvirus infections.Current research in microbial sciences · 2023Article
- Inspiratory hyperoxia suppresses lung cancer metastasis through a MYC/SLC1A5-dependent metabolic pathway.The European respiratory journal · 2022Article
- Small extracellular vesicles as key players in cancer development caused by human oncogenic viruses.Infectious agents and cancer · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Kaposi's sarcoma (KS) is a vascular neoplasm caused by infection of endothelial or endothelial precursor cells with the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8). Research efforts have focused on defining the molecular events explaining how KSHV promotes pathological angiogenesis and KS tumor formation. mTOR/HIF-1 is a fundamental pathway driving these processes through the upregulation of angiogenic and inflammatory proteins, including VEGF, ANGPTL4, and ANGPT2. Interestingly, HIF-1 has also been implicated in the upregulation of metabolic genes associated with aerobic glycolysis and the growth of solid tumors. However, whether HIF-1 plays a role in regulating cell metabolism in KS remains unexplored. Here, we show that the HIF-1 metabolic effector, pyruvate kinase 2 (PKM2), is upregulated upon KSHV infection of endothelial cells and is necessary to maintain aerobic glycolysis in infected cells. We further demonstrate that PKM2 regulates KS angiogenic phenotype by acting as a coactivator of HIF-1 and increasing the levels of HIF-1 angiogenic factors, including VEGF. Indeed, inhibition of PKM2 expression blocked endothelial cell migration and differentiation and the angiogenic potential of KSHV-infected cells. We also investigated whether PKM2 regulates the angiogenic dysregulation induced by the KSHV-encoded G protein-coupled receptor (vGPCR), a viral oncogene that promotes Kaposi's sarcomagenesis through the upregulation of HIF angiogenic factors. Interestingly, we found that PKM2 controls vGPCR-induced VEGF paracrine secretion and vGPCR oncogenesis. Our findings provide a molecular mechanism for how HIF-1 dysregulation fuels both angiogenesis and tumor metabolism in KS and support further investigations on therapeutic approaches targeting HIF-1 and PKM2 for KS treatment.
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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.