ArticleThe American journal of pathology2007
Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Trial
- A stromal PAI1-tPA axis orchestrates immunosuppression in pancreatic cancer.Science advances · 2026Article
- Tissue Plasminogen Activator as an Approved Strategy for Ischemic Stroke: A Review of tPA's Structure, Mechanism of Action and the Novel Targeting Methods.Journal of molecular neuroscience : MN · 2025Review
- To construct and validate a risk score model of angiogenesis-related genes to predict the prognosis of hepatocellular carcinoma.Scientific reports · 2025Article
- Human epididymis protein 4-annexin II binding promotes aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis.Communications biology · 2025Article
- Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres.International journal of molecular sciences · 2024Article
- Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.Molecular oncology · 2024Article
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- Molecular Mechanisms of Inhibitory Effects of Bovine Lactoferrin on Invasion of Oral Squamous Cell Carcinoma.Pharmaceutics · 2023Article
- CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells.Frontiers in cell and developmental biology · 2023Article
- Tissue Plasminogen Activator as a Possible Indicator of Breast Cancer Relapse: A Preliminary, Prospective Study.Journal of clinical medicine · 2022Article
- Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.American journal of physiology. Cell physiology · 2021Review
- Review
- Review
- The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?Cellular and molecular life sciences : CMLS · 2019Review
- PAI1 blocks NMDA receptor-mediated effects of tissue-type plasminogen activator on cell signaling and physiology.Journal of cell science · 2018Article
- Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer.Frontiers in oncology · 2018Review
- Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.Journal of natural products · 2017Article
- Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.Scientific reports · 2015Article
- COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer.Molecular cancer · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue plasminogen activator (tPA) is overexpressed in pancreatic ductal carcinoma and is involved in tumor progression. This effect is probably mediated through the activation of angiogenesis, cell invasion, and cell proliferation. Previous studies support the notion that the effects of tPA on cell invasion require its proteolytic activity. Here, we report the molecular mechanism responsible for the proliferative effects of tPA on pancreatic tumor cells. tPA activates the extracellular signal-regulated kinase 1/2 signaling pathway in a manner that is independent of its catalytic activity. We also show that at least two membrane receptors, epidermal growth factor receptor and annexin A2, which are overexpressed in pancreatic cancer, are involved in the transduction of tPA signaling in pancreatic tumors. This observation suggests the establishment of an amplification loop in tumor cell proliferation. Double immunofluorescence experiments showed co-localization of tPA/epidermal growth factor receptor and tPA/annexin A2 in pancreas cancer cells. These results add novel insights into the non-catalytic functions of tPA in cancer and the molecular mechanisms behind the effects of this protease on cell proliferation, including a role for epidermal growth factor receptor.
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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.