ArticleMolecular biology of the cell2013
Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Computational insights into cancer stem cell dynamics and the urokinase plasminogen activation pathway.Journal of biosciences · 2026Article
- PAI-1 deficiency drives pulmonary vascular smooth muscle remodeling and pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1.Biology direct · 2024Article
- Investigation of key signaling pathways and appropriate diagnostic biomarkers selection between non-invasive to invasive stages in pancreatic cancer: a computational observation.Journal of medicine and life · 2022Article
- Identification of Candidate Therapeutic Target Genes and Profiling of Tumor-Infiltrating Immune Cells in Pancreatic Cancer via Integrated Transcriptomic Analysis.Disease markers · 2022Article
- Article
- FOLFIRINOX regulated tumor immune microenvironment to extend the survival of patients with resectable pancreatic ductal adenocarcinoma.Gland surgery · 2020Article
- Identification of potential hub genes associated with the pathogenesis and prognosis of pancreatic duct adenocarcinoma using bioinformatics meta-analysis of multi-platform datasets.Oncology letters · 2019Article
- Review
- microRNA-26a-5p Promotes Proliferation and Migration of Osteosarcoma Cells by TargetingOncoTargets and therapy · 2019Article
- Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells.Molecular medicine reports · 2018Article
- Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker originate from CD44-negative cells.Oncotarget · 2018Article
- Urokinase-type plasminogen activator (uPA) is critical for progression of tuberous sclerosis complex 2 (TSC2)-deficient tumors.The Journal of biological chemistry · 2017Article
- Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells.Biomedicines · 2017Review
- Current status of biomarker and targeted nanoparticle development: The precision oncology approach for pancreatic cancer therapy.Cancer letters · 2017Article
- Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis.Disease markers · 2017Article
- Article
- uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy.Oncotarget · 2016Review
- Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress.Oncotarget · 2016Article
- Urokinase-type Plasminogen Activator (uPA) Promotes Angiogenesis by Attenuating Proline-rich Homeodomain Protein (PRH) Transcription Factor Activity and De-repressing Vascular Endothelial Growth Factor (VEGF) Receptor Expression.The Journal of biological chemistry · 2016Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the underlying reasons for this lethality is believed to be the presence of cancer stem cells (CSC), which impart chemoresistance and promote recurrence, but the mechanisms responsible are unclear. Recently the poor prognosis of PDAC has been correlated with increased expression of urokinase plasminogen activator (uPA). In the present study we examine the role of uPA in the generation of PDAC CSC. We observe a subset of cells identifiable as a side population (SP) when sorted by flow cytometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possess the properties of CSC. A large fraction of these SP cells are CD44 and CD24 positive, are gemcitabine resistant, possess sphere-forming ability, and exhibit increased tumorigenicity, known characteristics of cancer stemness. Increased tumorigenicity and gemcitabine resistance decrease after suppression of uPA. We observe that uPA interacts directly with transcription factors LIM homeobox-2 (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote cancer stemness. uPA regulates Lhx2 expression by suppressing expression of miR-124 and p53 expression by repressing its promoter by inactivating HOXA5. These results demonstrate that regulation of gene transcription by uPA contributes to cancer stemness and clinical lethality.
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