ArticleGut2007
Activation of the epidermal growth factor signalling pathway by tissue plasminogen activator in pancreas cancer cells.
Article in Gut, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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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
14 citing papers in PubMed, 28 citations in OpenAlex.
- Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses.Journal of neuroinflammation · 2021Article
- Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.Journal of natural products · 2017Article
- Translational initiatives in thrombolytic therapy.Frontiers of medicine · 2017Review
- New Insights into Diabetes Cell Therapy.Current diabetes reports · 2016Review
- Inhibition of progression of PanIN through antagonizing EGFR.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD.Respiratory research · 2011Article
- Tissue plasminogen activator prevents white matter damage following stroke.The Journal of experimental medicine · 2011Article
- Regulation of proteinases during mouse peri-implantation development: urokinase-type plasminogen activator expression and cross talk with matrix metalloproteinase 9.Reproduction (Cambridge, England) · 2011Article
- tPA is a potent mitogen for renal interstitial fibroblasts: role of beta1 integrin/focal adhesion kinase signaling.The American journal of pathology · 2010Article
- IL-1beta induces expression of matrix metalloproteinase-9 and cell migration via a c-Src-dependent, growth factor receptor transactivation in A549 cells.British journal of pharmacology · 2010Article
- Activated protein C enhances cell motility of endothelial cells and MDA-MB-231 breast cancer cells by intracellular signal transduction.Experimental cell research · 2010Article
- Review
- Molecular biology of pancreatic cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2008Review
- Novel actions of tissue-type plasminogen activator in chronic kidney disease.Frontiers in bioscience : a journal and virtual library · 2008Review
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 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTissue plasminogen activator (tPA) is the major activator of plasminogen in plasma. This serine protease is overexpressed by exocrine pancreas tumour cells, where it promotes tumour cell proliferation, growth, and invasion. Here we have explored the signalling pathways used by tPA to activate the proliferation of pancreatic cancer cells.
methodsTranscriptional profiling on cDNA micro arrays was used to analyse the pattern of gene expression in response to tPA compared to the response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF). Results were confirmed using different biochemical assays in which specific kinase inhibitors or RNA interference were used.
resultsTranscriptional profiling showed that tPA modulates the expression of a set of genes commonly regulated by EGF, but distinct from the major set of genes modulated by PDGF. This suggested that tPA and EGF share common signalling pathways, a conclusion supported by further experimental evidence. Firstly, we found that tPA induced a rapid and transient phosphorylation of the EGFR. Secondly, specific EGFR kinase inhibitors, but not PDGFR kinase inhibitors, abolished the tPA induced phosphorylation of the ERK1/2 kinases and cell proliferation. The mitogenic activity of tPA was also inhibited by siRNA depletion of EGFR, thus confirming the involvement of this receptor in tPA triggered signalling. Thirdly, we show that the signalling and mitogenic effects of tPA require its proteolytic activity, the activity of the metalloprotease-9 and active hb-EGF.
conclusionOur results suggest that tPA induces proliferation by triggering a proteolytic cascade that sequentially activates plasmin, metalloprotease-9 (MMP-9) and hb-EGF. These events are required to activate the EGFR signalling pathway and cell proliferation.
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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.