ArticlePloS one2011
Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Article
- Kaposi Sarcoma Herpes Virus Reprograms Mesenchymal Cell Glycosylation to control platelet-derived growth factor receptor A signaling.bioRxiv : the preprint server for biology · 2026Article
- The bittersweet link between glucose metabolism, cellular microenvironment and viral infection.Virulence · 2025Review
- Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.Frontiers in cell and developmental biology · 2025Review
- Targeting hypoxia-inducible factors in malignancies caused by Kaposis sarcoma associated herpesvirus.Global health & medicine · 2024Article
- Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.PLoS pathogens · 2024Article
- Hypoxia and HIF-1α promote lyticJournal of virology · 2023Article
- KDM5 family of demethylases promotes CD44-mediated chemoresistance in pancreatic adenocarcinomas.Scientific reports · 2023Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.PLoS pathogens · 2023Article
- Hypoxia and hypoxia-inducible factors in Kaposi sarcoma-associated herpesvirus infection and disease pathogenesis.Journal of medical virology · 2023Review
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.bioRxiv : the preprint server for biology · 2023Article
- Cancers associated with human gammaherpesviruses.The FEBS journal · 2022Review
- Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma.International journal of molecular sciences · 2022Article
- Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2022Review
- Prognostic value, immune signature and molecular mechanisms of the APOBEC family members APOBEC1, APOBEC3A, APOBEC3G and APOBEC3H in pancreatic adenocarcinoma.Frontiers in molecular biosciences · 2022Article
- Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis.Cell reports · 2021Article
- Impact of Hypoxia over Human Viral Infections and Key Cellular Processes.International journal of molecular sciences · 2021Review
- Metabolic landscapes in sarcomas.Journal of hematology & oncology · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundKaposi's sarcoma (KS) is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF), essential for KS development. However, the origin of VEGF in this tumor remains unclear. METHODOLOGY/PRINCIPAL
findingsHere we report that the KSHV G protein-coupled receptor (vGPCR) upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ) that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression. CONCLUSIONS/SIGNIFICANCE: Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.
Indexed as
Identifiers
What OpenQuestion holds
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.