ArticleNeoplasia (New York, N.Y.)2009
Transcriptional regulation of urokinase-type plasminogen activator receptor by hypoxia-inducible factor 1 is crucial for invasion of pancreatic and liver cancer.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 73 citations in OpenAlex.
- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment.Medical oncology (Northwood, London, England) · 2024Review
- Endothelial-specific Enhancer as a Cis Element ofCurrent pharmaceutical design · 2024Review
- Travelling under pressure - hypoxia and shear stress in the metastatic journey.Clinical & experimental metastasis · 2023Review
- NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment.Frontiers in pharmacology · 2023Review
- Hypoxia: molecular pathophysiological mechanisms in human diseases.Journal of physiology and biochemistry · 2022Review
- 3D In Vivo Models for Translational Research on Pancreatic Cancer: The Chorioallantoic Membrane (CAM) Model.Cancers · 2022Review
- Review
- Review
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- MIF promotes cell invasion by the LRP1-uPAR interaction in pancreatic cancer cells.Frontiers in oncology · 2022Article
- Epigenetic Regulation During Hypoxia and Its Implications in Cancer.Sub-cellular biochemistry · 2022Article
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- HIF-DependentFrontiers in genetics · 2021Article
- HIF-1α Metabolic Pathways in Human Cancer.Advances in experimental medicine and biology · 2021Review
- An ATFCancer biology & medicine · 2020Article
- Hypoxia and Bone Metastatic Disease.Current osteoporosis reports · 2017Review
- Current status of biomarker and targeted nanoparticle development: The precision oncology approach for pancreatic cancer therapy.Cancer letters · 2017Article
- The impact of hypoxia on tumor-associated macrophages.The Journal of clinical investigation · 2016Review
- Preparation and antitumor effect of a toxin-linked conjugate targeting vascular endothelial growth factor receptor and urokinase plasminogen activator.Experimental biology and medicine (Maywood, N.J.) · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angioinvasion is critical for metastasis with urokinase-type plasminogen activator receptor (uPAR) and tumor hypoxia-activated hypoxia-inducible factor 1 (HIF-1) as key players. Transcriptional control of uPAR expression by HIF has never been reported. The aim of the present study, therefore, was to test whether tumor hypoxia-induced HIF expression may be linked to transcriptional activation of uPAR and dependent angioinvasion. We used human pancreatic cancer cells and a model of parental and derived HIF-1beta-deficient mouse liver cancer cell lines and performed Northern blot analysis, nuclear runoff assays, electrophoretic mobility shift assay, polymerase chain reaction-generated deletion mutants, luciferase assays, Matrigel invasion assays, and in vivo angioinvasion assays in the chorioallantoic membrane of fertilized chicken eggs. Urokinase-type plasminogen activator receptor promoter analysis resulted in four putative HIF binding sites. Hypoxia strongly induced de novo transcription of uPAR mRNA. With sequential deletion mutants of the uPAR promoter, it was possible to identify one HIF binding site causing a nearly 200-fold increase in luciferase activity. Hypoxia enhanced the number of invading tumor cells in vitro and in vivo. In contrast, HIF-1beta-deficient cells failed to upregulate uPAR expression, to activate luciferase activity, and to invade on hypoxia. Taken together, we show for the first time that uPAR is under transcriptional control of HIF and that this is important for hypoxia-induced metastasis.
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