ArticleCell2009
Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.
Article in Cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 408 papers.
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
408 citing papers in PubMed, 804 citations in OpenAlex.
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- Nanosystem-Mediated Intercellular Crosstalk Modulation in the Tumor Microenvironment for Enhanced Cancer Immunotherapy.Drug design, development and therapy · 2026Review
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
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- 3D bioprinting innovations: a new frontier in breast cancer research.Medical oncology (Northwood, London, England) · 2025Review
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- Understanding Endometriosis: A Broad Review of Its Causes, Management, and Impact.International journal of molecular sciences · 2025Review
- Within and beyond the tumor: Mechanisms of glioblastoma-induced immunosuppression.Neuro-oncology advances · 2025Review
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Activated T Cells Break Tumor Immunosuppression by Macrophage Reeducation.Cancer discovery · 2025Article
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- Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies.Biomarker research · 2025Review
- Metabolic reprogramming and interventions in angiogenesis.Journal of advanced research · 2025Review
- Thylakoids for enhanced photodynamic therapy in hypoxic tumours.Science and technology of advanced materials · 2025Review
- Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes.ImmunoTargets and therapy · 2025Review
- Vascular regional analysis unveils differential responses to anti-angiogenic therapy in pancreatic xenografts through macroscopic photoacoustic imaging.Theranostics · 2025Article
348 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 4 countries.
Funding
Abstract
A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2(+/-) mice. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation and inhibited tumor cell invasion, intravasation, and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent cell type, lacking filopodia and arrayed in a phalanx formation. This transition relied on HIF-driven upregulation of (soluble) VEGFR-1 and VE-cadherin. Thus, decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial cells to readjust their shape and phenotype to restore oxygen supply. Inhibition of PHD2 may offer alternative therapeutic opportunities for anticancer therapy.
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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.