Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer

This research highlights the multifunctional role of uPA in pancreatic cancer as a regulator of stemness and chemoresistance. uPA is found to be physically associated with the transcription factors Lhx2 and HOXA5 in the nucleus and regulated expression of p53.

• Publication year

  2013

• Venue

  Molecular Biology of the Cell

• Publication date

  2013-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1091/mbc.E12-04-0306PMID 23864708PMCID 3756915
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Retraction Note to: Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

  2014cited by this paper
• RETRACTED ARTICLE: Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

  2013cited by this paper
• Tumor-stromal interactions in pancreatic cancer.

  2013cited by this paper
• Tumor-stromal interactions in pancreatic cancer.

  2013cited by this paper
• Mesenchymal stem cells regulate epithelial–mesenchymal transition and tumor progression of pancreatic cancer cells

  2013cited by this paper
• Expression of Urokinase‐Type Plasminogen Activator (uPA), its Receptor (uPAR), and Inhibitor (PAI‐1) in Human Breast Carcinomas and Their Clinical Relevance

  2012cited by this paper
• LHX2 deregulation by juxtaposition with the IGH locus in a pediatric case of chronic myeloid leukemia in B-cell lymphoid blast crisis.

  2012cited by this paper
• Signaling pathways mediating epithelial- mesenchymal crosstalk in pancreatic cancer: Hedgehog, Notch and TGFβ

  2012cited by this paper
• The nuclear translocation of endostatin is mediated by its receptor nucleolin in endothelial cells

  2012cited by this paper
• Pancreatic cancer stem cell and mesenchymal stem cell

  2012cited by this paper
• Cancer stem cells: an evolving concept

  2012cited by this paper
• Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Regulation of WNT/β-Catenin Signaling Is Enhanced in Irradiated Medulloblastoma Cells*

  2012cited by this paper
• ETS1 promotes chemoresistance and invasion of paclitaxel-resistant, hormone-refractory PC3 prostate cancer cells by up-regulating MDR1 and MMP9 expression.

  2012cited by this paper
• Biological and clinical relevance of stem cells in pancreatic adenocarcinoma

  2012cited by this paper
• DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA.

  2012cited by this paper
• The Pancreas Cancer Microenvironment

  2012cited by this paper
• Screening of LHX2 in patients presenting growth retardation with posterior pituitary and ocular abnormalities.

  2012cited by this paper
• Loss of Brain-enriched miR-124 MicroRNA Enhances Stem-like Traits and Invasiveness of Glioma Cells*

  2012cited by this paper
• Urokinase plasminogen activator receptor induced non-small cell lung cancer invasion and metastasis requires NHE1 transporter expression and transport activity

  2012cited by this paper
• Genome-wide identification of OTP gene as a novel methylation marker of breast cancer.

  2012cited by this paper
• Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1

  2011cited by this paper
• Inhibition of epithelial-to-mesenchimal transition

  2011cited by this paper
• Activation of pro-uPA is critical for initial escape from the primary tumor and hematogenous dissemination of human carcinoma cells.

  2011cited by this paper
• Clinical applications of the urokinase receptor (uPAR) for cancer patients.

  2011cited by this paper
• Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells.

  2011cited by this paper
• Suppression of the uPAR–uPA System Retards Angiogenesis, Invasion, and In Vivo Tumor Development in Pancreatic Cancer Cells

  2011influential reference
• Under stress: p53 controls EMT and stemness in pancreatic epithelial cells

  2011cited by this paper
• The urokinase-type plasminogen activator and the generation of inhibitors of urokinase activity and signaling.

  2011cited by this paper
• Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis

  2011cited by this paper
• uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy.

  2011influential reference
• Pancreatic Cancer Cells Resistant to Chemoradiotherapy Rich in “Stem-Cell-Like” Tumor Cells

  2011cited by this paper
• Downregulation of uPA/uPAR inhibits intermittent hypoxia-induced epithelial-mesenchymal transition (EMT) in DAOY and D283 medulloblastoma cells.

  2011cited by this paper
• Development of novel therapeutics targeting the urokinase plasminogen activator receptor (uPAR) and their translation toward the clinic.

  2011cited by this paper
• Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

  2011cited by this paper
• Pancreatic cancer stem cells – update and future perspectives

  2010influential reference
• Ets-1 expression and gemcitabine chemoresistance in pancreatic cancer cells

  2010cited by this paper
• Inactivation of p53 in breast cancers correlates with stem cell transcriptional signatures

  2010cited by this paper
• Modulators of the urokinase-type plasminogen activation system for cancer

  2010cited by this paper
• A role of the LIM-homeobox gene Lhx2 in the regulation of pituitary development.

  2010cited by this paper
• Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics.

  2010cited by this paper
• Cyclic Expression of Lhx2 Regulates Hair Formation

  2010cited by this paper
• Tumour budding, uPA and PAI‐1 are associated with aggressive behaviour in colon cancer

  2010cited by this paper
• Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells

  2010influential reference
• CD44‐positive cells are responsible for gemcitabine resistance in pancreatic cancer cells

  2009cited by this paper
• Urokinase plasminogen activator system as a potential target for cancer therapy.

  2009influential reference
• Urokinase expression in course of benign and malignant mammary lesions: comparison between nodular and healthy tissues

  2009cited by this paper
• A Pilot Study of Urokinase-Type Plasminogen Activator (uPA) Overexpression in the Brush Cytology of Patients with Malignant Pancreatic or Biliary Strictures

  2009cited by this paper
• Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression

  2009cited by this paper
• Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications

  2009cited by this paper
• Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion

  2009cited by this paper
• Nuclear translocation of urokinase-type plasminogen activator.

  2008influential reference
• Lhx2 Expression Promotes Self-Renewal of a Distinct Multipotential Hematopoietic Progenitor Cell in Embryonic Stem Cell-Derived Embryoid Bodies

  2008cited by this paper
• Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer: A Randomized Controlled Trial

  2008influential reference
• Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.

  2007cited by this paper
• Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.

  2007cited by this paper
• Intraperitoneal Injection of a Hairpin RNA–Expressing Plasmid Targeting Urokinase-Type Plasminogen Activator (uPA) Receptor and uPA Retards Angiogenesis and Inhibits Intracranial Tumor Growth in Nude Mice

  2007cited by this paper
• The role of site accessibility in microRNA target recognition

  2007cited by this paper
• Establishment of Clonal Colony-Forming Assay for Propagation of Pancreatic Cancer Cells With Stem Cell Properties

  2007influential reference
• Down-regulation of uPAR and uPA activates caspase-mediated apoptosis and inhibits the PI3K/AKT pathway.

  2007cited by this paper
• RNAi-mediated downregulation of urokinase plasminogen activator and its receptor in human meningioma cells inhibits tumor invasion and growth.

  2006cited by this paper
• Post-transcriptional Control of Cited2 by Transforming Growth Factor β

  2006cited by this paper
• Catalog of gene expression in adult neural stem cells and their in vivo microenvironment.

  2006cited by this paper
• Combination Therapy Using Gemcitabine and Radioimmunotherapy in Nude Mice with Small Peritoneal Metastases of Colonic Origin

  2006influential reference
• Lhx2—decisive role in epithelial stem cell maintenance, or just the “tip of the iceberg”?

  2006cited by this paper
• Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growth.

  2004cited by this paper
• Clinical significance of urokinase‐type plasminogen activator receptor (uPAR) expression in cancer

  2004cited by this paper
• MicroRNA Targets in Drosophila

  2003cited by this paper
• Expression of antisense uPAR and antisense uPA from a bicistronic adenoviral construct inhibits glioma cell invasion, tumor growth, and angiogenesis

  2003cited by this paper
• Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression.

  2003cited by this paper
• MicroRNA targets in Drosophila

  2003cited by this paper
• Evaluation of urinary plasminogen activator, its receptor, matrix metalloproteinase-9, and von Willebrand factor in pancreatic cancer.

  2003cited by this paper
• uPAR: a versatile signalling orchestrator

  2002cited by this paper
• Suppression of glioma invasion and growth by adenovirus-mediated delivery of a bicistronic construct containing antisense uPAR and sense p16 gene sequences

  2002cited by this paper
• Multipotent hematopoietic progenitor cells immortalized by Lhx2 self-renew by a cell nonautonomous mechanism.

  2001cited by this paper
• HOXA5 Regulates Expression of the Progesterone Receptor*

  2000influential reference
• Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin.

  1999cited by this paper
• The Ets‐1 and Ets‐2 transcription factors activate the promoters for invasion‐associated urokinase and collagenase genes in response to epidermal growth factor

  1998cited by this paper
• In vitro inhibition of human glioblastoma cell line invasiveness by antisense uPA receptor

  1997cited by this paper
• Expression and localization of urokinase-type plasminogen activator receptor in human gliomas.

  1994cited by this paper
• A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.

  1992influential reference
• Tumorigenesis and Neoplastic Progression Influence of Hoxa5 on p53 Tumorigenic Outcome in Mice DNA

  year unknowncited by this paper

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  2024cites this paper
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  2023cites this paper
• Noncoding ribonucleic acid for pancreatic cancer therapy

  2022cites this paper
• Investigation of key signaling pathways and appropriate diagnostic biomarkers selection between non-invasive to invasive stages in pancreatic cancer: a computational observation

  2022cites this paper
• Identification of Candidate Therapeutic Target Genes and Profiling of Tumor-Infiltrating Immune Cells in Pancreatic Cancer via Integrated Transcriptomic Analysis

  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
• Molecular Mechanisms of Action of Myricetin in Cancer.

  2020cites this paper
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  2020cites this paper
• FOLFIRINOX regulated tumor immune microenvironment to extend the survival of patients with resectable pancreatic ductal adenocarcinoma.

  2020cites this paper
• Nucleolin Is a Functional Binding Protein for Salinomycin in Neuroblastoma Stem Cells.

  2019cites this paper
• Deciphering The Potential Role of Hox Genes in Pancreatic Cancer

  2019cites this paper
• The Role of the Urokinase-Type Plasminogen Activator System In Tumor Progression

  2019cites this paper
• Screening and identification of hub genes in pancreatic cancer by integrated bioinformatics analysis

  2019cites this paper
• Identification of potential hub genes associated with the pathogenesis and prognosis of pancreatic duct adenocarcinoma using bioinformatics meta-analysis of multi-platform datasets

  2019cites this paper
• microRNA-26a-5p Promotes Proliferation and Migration of Osteosarcoma Cells by Targeting HOXA5 in vitro and in vivo

  2019cites this paper
• Development of Ligand-Directed Drug-Loaded Liposomes to Target Heterogeneous Tumour Cell Populations in Metastatic Breast Cancer

  2019cites this paper
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  2019cites this paper
• microRNA-26a-5p Promotes Proliferation and Migration of Osteosarcoma Cells by Targeting HOXA5 in vitro and in vivo

  2019cites this paper
• Diversity and functional evolution of the plasminogen activator system.

  2018cites this paper
• Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells

  2018cites this paper
• Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker originate from CD44-negative cells

  2018cites this paper
• The Urokinase Plasminogen Activator System in Human Cancers: An Overview of Its Prognostic and Predictive Role

  2018cites this paper
• [The urokinase-type plasminogen activator system and its role in tumor progression].

  2018cites this paper
• Multifaced Roles of the Urokinase System in the Regulation of Stem Cell Niches

  2018cites this paper
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  2017cites this paper
• Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

  2017influential citation
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
• [A plasminogen regulation system in brain tumors].

  2017cites this paper
• Enrichment and Interrogation of Cancer Stem Cells

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
• The urokinase-type plasminogen activator (uPA) system as a biomarker and therapeutic target in human malignancies

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
• MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas

  2015cites this paper
• Establishment of a pancreatic cancer stem cell model using the SW1990 human pancreatic cancer cell line in nude mice.

  2015cites this paper
• The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style

  2014cites this paper
• Mesenchymal to amoeboid transition is associated with stem-like features of melanoma cells

  2014influential citation
• c-Met signaling in the development of tumorigenesis and chemoresistance: potential applications in pancreatic cancer.

  2014cites this paper
• Pancreatic cancer stem cells: association with cell surface markers, prognosis, resistance, metastasis and treatment.

  2014cites this paper
• A role for tissue plasminogen activator in thrombotic thrombocytopenic purpura.

  2014cites this paper
• Brief overview of selected approaches in targeting pancreatic adenocarcinoma

  2014cites this paper
• Effect of Three Dimensional Culture of Porcine Endometrial Cells on Their Plasminogen Activity and Pre-implantation Embryo Development after Co-culture

  2014cites this paper
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  year unknowncites this paper