ArticleOncotarget2016
Human cytomegalovirus encoded chemokine receptor US28 activates the HIF-1α/PKM2 axis in glioblastoma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Prevalence of human cytomegalovirus in glioblastoma multiforme: a systematic review and meta-analysis.Journal of neuro-oncology · 2025Pooled it
- Targeting Human Cytomegalovirus as a Novel Approach for Glioblastoma Treatment.Pathogens (Basel, Switzerland) · 2025Review
- Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The Association Between Cytomegalovirus Infection and Increased Leukemia Incidence: A Retrospective Matched Cohort.Cureus · 2025Article
- Pyruvate kinase M2 modulates Japanese encephalitis virus replication in neuronal cells.The Journal of general virology · 2025Article
- Disruption of constitutive CXCR4 oligomers impairs oncogenic properties in lymphoid neoplasms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Plasma membrane rather than endosomal Gq signaling drives transcriptional activity by the viral chemokine receptor US28 in glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Role of cytomegalovirus in glioblastoma development: promoter or culprit?Virology journal · 2025Review
- Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34Antiviral research · 2025Article
- Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?Pathogens (Basel, Switzerland) · 2025Review
- Hexosaminidase B-driven cancer cell-macrophage co-dependency promotes glycolysis addiction and tumorigenesis in glioblastoma.Nature communications · 2024Article
- Clinical implications of cytomegalovirus in glioblastoma progression and therapy.NPJ precision oncology · 2024Review
- Contribution of carbohydrate-related metabolism in Herpesvirus infections.Current research in microbial sciences · 2023Article
- The potential of cold-shock promoters for the expression of recombinant proteins in microbes and mammalian cells.Journal, genetic engineering & biotechnology · 2022Review
- G-Protein Coupled Receptor Signaling and Mammalian Target of Rapamycin Complex 1 Regulation.Molecular pharmacology · 2022Review
- Article
- Article
- Research progress on the role of PKM2 in the immune response.Frontiers in immunology · 2022Review
- The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme.Frontiers in oncology · 2022Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human cytomegalovirus (HCMV) encoded chemokine receptor US28 promotes tumorigenesis through activation of various proliferative and angiogenic signaling pathways. Upon infection, US28 displays constitutive activity and signals in a G protein-dependent manner, hijacking the host's cellular machinery. In tumor cells, the hypoxia inducible factor-1α/pyruvate kinase M2 (HIF-1α/PKM2) axis plays an important role by supporting proliferation, angiogenesis and reprogramming of energy metabolism. In this study we show that US28 signaling results in activation of the HIF-1α/PKM2 feedforward loop in fibroblasts and glioblastoma cells. The constitutive activity of US28 increases HIF-1 protein stability through a Gαq-, CaMKII- and Akt/mTOR-dependent mechanism. Furthermore, we found that VEGF and lactate secretion are increased and HIF-1 target genes, glucose transporter type 1 (GLUT1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), involved in glucose metabolism, are upregulated in US28 expressing cells. In addition, PKM2 is phosphorylated and found to be in a tumor-associated dimeric state upon US28 expression. Also in HCMV-infected cells HIF-1 activity is enhanced, which in part is US28-dependent. Finally, increased proliferation of cells expressing US28 is abolished upon inhibition of the HIF-1α/PKM2 cascade. These data highlight the importance of HIF-1α and PKM2 in US28-induced proliferation, angiogenesis and metabolic reprogramming.
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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.