Affinage

PLAU

Urokinase-type plasminogen activator · UniProt P00749

Length
431 aa
Mass
48.5 kDa
Annotated
2026-06-10
67 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLAU encodes urokinase-type plasminogen activator (uPA), a secreted serine protease that functions through its receptor PLAUR/uPAR to drive cell proliferation, migration, invasion, and EMT across diverse cancers and to remodel the tumor microenvironment (PMID:33574243, PMID:32464191, PMID:36672610). Upon binding PLAUR, PLAU activates multiple downstream signaling cascades—MAPK/ERK (PMID:33574243, PMID:35567945), Akt/NF-κB (PMID:33574243, PMID:38229120, PMID:37067236), JAK-STAT3 (PMID:38663475), and Hippo-YAP (PMID:40639051)—and in esophageal and lung cancers it converts normal fibroblasts into cancer-associated fibroblasts, establishing pro-tumorigenic feedback loops via IL-8 and macrophage polarization (PMID:33574243, PMID:41264215, PMID:40639051). PLAU expression is controlled at multiple regulatory layers: transcriptionally by activating factors (Fra-1/AP-1 enhancers, YY1, FOSL1, NFE2L2/OSBPL3, the NIX-YY1 axis) and repressors (GATA6, miR-193a via Max/RXRα) (PMID:25200076, PMID:36524374, PMID:41264215, PMID:41687403, PMID:40639051, PMID:38702016, PMID:21670079); post-transcriptionally by m6A writers METTL3, WTAP, and ZC3H13 that stabilize PLAU mRNA (PMID:35567945, PMID:37094860, PMID:41377025); epigenetically through histone H4K12 lactylation at the PLAU locus, which links tumor metabolism to PLAU-mediated CD8+ T cell suppression (PMID:40826503); and translationally through repression by the STING-PERK-eIF2α axis (PMID:36496076). Beyond cancer, PLAU supports the suppressor function of regulatory T cells via STAT5 and ERK (PMID:23169000), and its catalytic activity is required for proper nervous-system development, since a catalytic-dead Plau D277N mutation produces autism-like behavioral deficits in mice (PMID:42170179). PLAU dysregulation causes Quebec platelet disorder, in which a 78-kb tandem duplication on chromosome 10q drives megakaryocyte-specific PLAU overexpression and >100-fold elevation of uPA in platelets (PMID:20007542, PMID:18988861, PMID:28301587).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 High

    Established that a defined genomic lesion at the PLAU locus causes human disease, linking PLAU dosage and tissue-specific transcriptional control to a bleeding phenotype.

    Evidence Copy number, linkage, and allele-specific expression analysis of a 78-kb tandem duplication in Quebec platelet disorder megakaryocytes

    PMID:18988861 PMID:20007542

    Open questions at the time
    • The cis-regulatory elements within the duplication responsible for megakaryocyte-specific dysregulation were not fully mapped
    • Mechanism of tissue specificity unresolved at this stage
  2. 2011 High

    Identified a microRNA-transcription factor circuit controlling PLAU during transformation, showing PLAU is a direct effector of invasive growth distinct from anchorage-independent growth.

    Evidence 3'UTR luciferase reporter, ChIP, RNAi, and invasion assays in isogenic breast epithelial and fibroblast transformation models

    PMID:21670079

    Open questions at the time
    • Did not address whether miR-193a regulation operates in established tumors in vivo
    • Downstream proteolytic substrates of de-repressed PLAU not defined
  3. 2012 Medium

    Extended PLAU function beyond cancer to immune regulation, showing it is required for regulatory T cell suppressor activity.

    Evidence Transcriptome correlation network with functional knockdown in human and murine Tregs and STAT5/ERK pathway analysis

    PMID:23169000

    Open questions at the time
    • Whether secreted protease activity or receptor signaling mediates the Treg effect not dissected
    • Single lab
  4. 2014 Medium

    Resolved the transcriptional architecture of the PLAU promoter, defining AP-1 enhancers and enhancer-derived transcription that feed productive Plau-001 mRNA in aggressive breast cancer.

    Evidence ChIP, pharmacological inhibition, RNAi, and promoter-enhancer dissection in MDA-MB231 cells

    PMID:25200076

    Open questions at the time
    • Function of enhancer-derived unstable RNAs not established
    • Generality beyond MDA-MB231 untested
  5. 2017 High

    Refined the QPD mechanism by demonstrating megakaryocyte-specific overexpression from the disease chromosome rather than simple gene-dosage effects, excluding the co-duplicated gene C10orf55.

    Evidence RNA-seq, allele-specific expression, and protein analysis in primary QPD megakaryocytes and platelets

    PMID:28301587

    Open questions at the time
    • Causal driver of type I interferon pathway down-regulation in QPD megakaryocytes unknown
    • Specific disrupted cis-elements still uncharacterized
  6. 2021 Medium

    Defined PLAU as a tumor-microenvironment remodeling factor that drives fibroblast-to-CAF conversion and reciprocal feedback, and confirmed pro-proliferative/EMT roles across cancers.

    Evidence Gain/loss-of-function, RNA-seq, cytokine assays, co-culture and pharmacological rescue in ESCC and PDAC; zebrafish vascular loss-of-function

    PMID:32464191 PMID:33574243 PMID:34354133

    Open questions at the time
    • uPAR/Akt/NF-κB feedback loop validated in single tumor type
    • Vascular and EMT roles rely on phenotypic readouts without deep pathway dissection
  7. 2022 Medium

    Established multilayered post-transcriptional and translational control of PLAU, identifying m6A-dependent mRNA stabilization and STING-mediated translational repression as opposing inputs.

    Evidence m6A/Me-RIP and mRNA stability assays (METTL3), secretory proteomics and pathway dissection (STING-PERK-eIF2α), promoter binding (YY1), and CRISPR-dCas9 bidirectional modulation

    PMID:35270021 PMID:35567945 PMID:36496076 PMID:36524374 PMID:36672610

    Open questions at the time
    • Which m6A readers decode PLAU methylation not identified
    • Crosstalk between transcriptional and translational control not integrated
  8. 2023 Medium

    Broadened the regulatory and signaling map of PLAU, adding further m6A writers and connecting PLAU to AKT/NF-κB-driven inflammation beyond cancer.

    Evidence Me-RIP/reporter assays (WTAP), miR-181b 3'UTR targeting with in vivo pulpitis model, and siRNA knockdown with NF-κB analysis in cholangiocarcinoma

    PMID:37067236 PMID:37094860 PMID:38154211

    Open questions at the time
    • Redundancy among m6A writers (METTL3/WTAP/ZC3H13) on PLAU not compared
    • Cholangiocarcinoma link is low-confidence with limited mechanistic detail
  9. 2024 Medium

    Expanded the PLAU signaling repertoire to JAK-STAT3 and identified protein partners (TM4SF1) and transcriptional repressors (GATA6) governing PLAU output.

    Evidence RNA-seq, Co-IP, STAT3 inhibitor and neutralizing-antibody rescue, and dual-luciferase promoter assays across head/neck and lung cancers

    PMID:38229120 PMID:38663475 PMID:38702016

    Open questions at the time
    • Whether TM4SF1 acts on secreted uPA or intracellular PLAU unclear
    • Each pathway demonstrated in a single tumor context
  10. 2025 Medium

    Integrated PLAU into metabolic-epigenetic and immune-evasion axes and established a causal requirement for uPA catalytic activity in nervous-system development.

    Evidence ChIP for H4K12 lactylation, CUT&RUN/MS/Co-IP (NIX-YY1), SPR (ApoE interaction), FOSL1 exosome ChIP/reporter, OSBPL3-NFE2L2 Co-IP, and a CRISPR D277N catalytic-dead knock-in mouse with behavioral phenotyping

    PMID:40639051 PMID:40826503 PMID:41264215 PMID:41475664 PMID:41687403 PMID:42170179

    Open questions at the time
    • Whether protease activity versus receptor signaling underlies each new role is largely unresolved
    • Neuronal substrate(s) of uPA proteolysis in development not identified
    • Many axes shown in single-lab single-context studies

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PLAU's catalytic protease activity versus its receptor-mediated (PLAUR) signaling is partitioned across its many reported roles, and which downstream proteolytic substrates execute its effects in each context.
  • No comprehensive substrate inventory tied to specific phenotypes
  • Relative contributions of transcriptional, m6A, lactylation, and translational control not integrated into one quantitative model
  • Most signaling axes lack independent cross-context replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 2 GO:0016787 hydrolase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-168256 Immune System 2
Partners
APOELRP1PLAURTM4SF1YY1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 miR-193a directly targets the 3' UTR of PLAU to suppress its expression; this suppression controls invasive growth (distinct from anchorage-independent growth, which is controlled via K-Ras). The transcription factors Max and RXRα bind directly to the miR-193a promoter and inhibit miR-193a expression, thereby de-repressing PLAU during cellular transformation. 3' UTR luciferase reporter assay, ChIP, RNAi, soft-agar and invasion assays in isogenic breast epithelial and fibroblast transformation models Cancer research High 21670079
2009 Quebec platelet disorder (QPD) is caused by a tandem duplication of a 78-kb genomic segment on chromosome 10q that includes PLAU; this duplication increases urokinase plasminogen activator mRNA levels specifically during megakaryocyte differentiation, causing >100-fold elevation of uPA in platelets without systemic fibrinolysis. Copy number variation analysis (Southern blotting, quantitative PCR), genetic linkage, allele-specific expression analysis in primary megakaryocytes Blood High 18988861 20007542
2017 The QPD PLAU duplication dysregulates PLAU in a megakaryocyte-specific manner: QPD megakaryocytes overexpress normal PLAU transcripts predominantly from the disease chromosome, whereas QPD leukocytes show only a ~3.9-fold increase consistent with gene dosage. C10orf55 (co-duplicated gene) is not overexpressed in QPD megakaryocytes or platelets. QPD megakaryocytes also show global down-regulation of the interferon type 1 pathway. RNA-seq, quantitative RT-PCR, allele-specific expression analysis, protein expression analysis in primary cells and cultured megakaryocytes from QPD donors PloS one High 28301587
2012 PLAU (urokinase plasminogen activator) is a critical gene for the suppressor function of human FOXP3+CD25+CD4+ regulatory T cells (Tregs). PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways, and is particularly important for memory Tregs. Inferred from high-time-resolution transcriptome correlation network; validated by functional knockdown/loss-of-function experiments in human and murine Tregs with suppressor function readout, STAT5/ERK pathway analysis Molecular systems biology Medium 23169000
2014 Fra-1/AP-1 controls transcription of PLAU (uPA) in aggressive breast cancer (MDA-MB231) through two AP-1 enhancers located -1.9 kb (ABR-1.9) and -4.1 kb (ABR-4.1) upstream of the Plau-001 transcription start site. RNA Pol II is recruited not only to the Plau-001 TSS but also to these upstream enhancers, where it transcribes short unstable RNAs that track toward the TSS before converting to productive Plau-001 mRNA. A minority of Pol II molecules transcribes a low-abundance mRNA (Plau-004) from the ABR-1.9 domain, whose expression is tempered by Fra-1. ChIP, pharmacological inhibition, RNAi, promoter-enhancer dissection in MDA-MB231 cells Nucleic acids research Medium 25200076
2022 STING pathway activation inhibits PLAU translation via the STING-PERK-eIF2α signaling axis. Suppression of PLAU by STING activation inhibits cancer cell migration and invasion. Quantitative proteomics of secretory proteins, mechanistic analysis of STING-PERK-eIF2α pathway, functional migration/invasion assays The Journal of biological chemistry Medium 36496076
2021 PLAU secreted by ESCC tumor cells promotes conversion of normal fibroblasts to inflammatory cancer-associated fibroblasts (CAFs) via the uPAR/Akt/NF-κB pathway, leading to upregulation and secretion of IL-8. IL-8 secreted by CAFs in turn promotes high PLAU expression in tumor cells, creating a positive feedback loop. PLAU also promotes ESCC cell proliferation via the MAPK pathway and migration via upregulation of Slug and MMP9. Loss-of-function and gain-of-function experiments, RNA sequencing, cytokine detection, RT-qPCR, pharmacological inhibition (U0126), co-culture assays Cell death discovery Medium 33574243
2022 METTL3 upregulates PLAU mRNA in an m6A-dependent manner, stabilizing PLAU mRNA to promote angiogenesis and metastasis via the MAPK/ERK pathway in colorectal cancer. m6A methylation assays, mRNA stability assays, functional in vitro and in vivo metastasis assays, MAPK/ERK pathway analysis Biochemical and biophysical research communications Medium 35567945
2023 WTAP mediates m6A modification of PLAU mRNA to stabilize it and increase PLAU expression in laryngeal squamous cell carcinoma, promoting cell migration, invasion, and proliferation. Luciferase reporter assay, methylated-RNA immunoprecipitation (Me-RIP), qRT-PCR, Western blotting, CCK-8/EdU/Transwell functional assays Annals of clinical and laboratory science Medium 37094860
2022 The transcription factor YY1 regulates PLAU mRNA expression by binding to the core PLAU promoter in cervical cancer cells. Core promoter mapping, transcription factor binding assay, RT-qPCR, functional knockdown assays for migration and invasion Oncology reports Medium 36524374
2024 GATA6 transcriptionally represses PLAU expression in lung squamous cell carcinoma cells. PLAU promotes LUSC cell proliferation and migration. Dual-luciferase reporter assay, RT-PCR, immunoblotting, EdU incorporation, Transwell assays, RNA-seq Biochimica et biophysica acta. Molecular cell research Medium 38702016
2024 PLAU interacts with TM4SF1 to promote activation of Akt signaling, conferring growth, survival, and cisplatin resistance to ARID1A-depleted NSCLC cells. Anti-TM4SF1 neutralizing antibody reversed these effects. Co-immunoprecipitation (interaction), overexpression and knockdown studies, Akt signaling analysis, in vivo xenograft models, neutralizing antibody treatment Biology direct Medium 38229120
2022 CRISPR-dCas9-mediated downregulation of PLAU in high-expressing MDA-MB-231 breast cancer cells (using DNMT3A/3L-KRAB) decreased cell proliferation, while CRISPR-dCas9-VP64-mediated upregulation in low-expressing MCF-7 cells significantly increased aggressiveness and invasion, functionally validating PLAU as an oncogene in breast cancer. CRISPR-dCas9 epigenetic modulation (transcriptional activation and repression), cell proliferation and invasion assays Biomedicines Medium 36672610
2023 PLAU activates the AKT/NF-κB signaling pathway; miR-181b targets PLAU to inhibit this axis and reduce pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) expression in dental pulp cells. PLAU knockdown reversed the pro-inflammatory effect of miR-181b inhibition, and PLAU overexpression prevented the anti-inflammatory effects of miR-181b mimics. Dual-luciferase gene reporter assay (miR-181b→PLAU targeting), RNA sequencing, Western blotting, qRT-PCR, in vivo rat pulpitis model International immunopharmacology Medium 38154211
2021 PLAU promotes proliferation via the MAPK pathway and promotes EMT progression (supported by Western blot evidence) in pancreatic ductal adenocarcinoma cells. In vitro cell proliferation/migration assays, Western blot for EMT markers, shRNA knockdown, immunohistochemistry in patient samples European journal of pharmacology Low 32464191
2024 PLAU promotes head and neck cancer cell proliferation and metastasis via the JAK-STAT3 signaling pathway; pharmacological inhibition of STAT3 (S3I-201) reversed the effects of ectopic PLAU expression. RNA-seq pathway identification, Western blotting, STAT3 inhibitor rescue assay, xenograft models Experimental cell research Medium 38663475
2021 Functional loss of PLAU (plau) in zebrafish synergistically impairs intersegmental vessel formation with loss of EP300 (ep300a), resulting in vascular occlusion phenotype, establishing PLAU's role in vascular development. Zebrafish morpholino/CRISPR loss-of-function, vascular phenotype assessment (intersegmental vessel formation) Scientific reports Low 34354133
2022 AQR promotes endothelial cell senescence and upregulates PLAU as a downstream effector; PLAU knockdown rescues senescence-related phenotypes, endothelial cell activation, and inflammation in models induced by AQR overexpression or TNF-α, establishing AQR/PLAU as a signaling axis in hyperglycemia-induced endothelial senescence. AQR overexpression/knockdown transcriptomic analyses, PLAU knockdown, senescence-associated β-galactosidase staining, CDKN1A/P21 measurement, colony formation, cell cycle analysis International journal of molecular sciences Medium 35270021
2023 PLAU activates the NF-κB signaling pathway in cholangiocarcinoma cells to drive malignant phenotypes; PLAU knockdown suppressed NF-κB activation and inhibited proliferation, migration, and tumor growth in vitro and in vivo. PLAU siRNA knockdown, NF-κB pathway analysis, proliferation/migration/apoptosis assays, in vivo mouse tumor model Cell biology international Low 37067236
2021 PLAU promotes nucleus pulposus chondrocyte apoptosis in intervertebral disc degeneration through activation of the HIPPO signaling pathway, increasing phosphorylation levels of MST1/2, LATS1/2, and YAP. In vitro and in vivo experiments, phosphorylation analysis of HIPPO pathway components, apoptosis assays Pathology, research and practice Low 40700932
2025 In hypoxia-associated lung adenocarcinoma, HIF1A recruits the mitophagy protein NIX for a non-canonical nuclear role: under hypoxia, NIX translocates to the nucleus, interacts with the PLAU transcription factor YY1, and enhances YY1 binding to the PLAU promoter, thereby upregulating PLAU. PLAU then activates Hippo-YAP signaling upon binding to PLAUR on lung fibroblasts, driving CAF activation. CUT&RUN, mass spectrometry, immunofluorescence, co-immunoprecipitation, Western blotting, ELISA, in vivo studies International immunopharmacology Medium 40639051
2025 FOSL1 (delivered by CAF-derived exosomes) transcriptionally activates PLAU expression in hepatocellular carcinoma cells, as validated by ChIP and luciferase assays. PLAU depletion suppressed HCC malignant phenotypes and decreased pro-tumorigenic M2 macrophage polarization. ChIP assay, luciferase reporter assay, exosome co-culture, functional migration/proliferation/invasion assays, macrophage polarization assays Applied biochemistry and biotechnology Medium 41264215
2025 Apolipoprotein E protein interacts with PLAU as a high-affinity interactor (identified by SPIDER technology and surface plasmon resonance), and apoE suppresses TGF-β/Smad-driven fibroblast activation via dual LRP1/PLAU co-engagement, attenuating α-SMA, collagen 1, and fibronectin expression. SPIDER technology, surface plasmon resonance (SPR), single-cell transcriptomics, TGF-β/Smad pathway analysis, Apoe-/- mouse models, recombinant protein rescue Journal of advanced research Medium 41475664
2025 PLAU activates the Hippo-YAP signaling pathway upon binding to its receptor PLAUR on lung fibroblasts, promoting CAF activation in collagenic lung adenocarcinoma. Western blotting, immunohistochemistry, co-culture systems, in vivo studies, Upamostat treatment International immunopharmacology Low 40639051
2025 Plau D277N mutation (impairing catalytic activity of uPA) in mice causes autism spectrum disorder-like traits including high anxiety, impaired social behavior, slowed spatial memory learning, and impaired stress adaptation, demonstrating that uPA proteolytic activity is required for adequate positioning of cellular components in the developing nervous system. CRISPR/Cas9 knock-in mouse model (D277N), behavioral assays (social activity, anxiety, memory, problem-solving), brain histology Frontiers in cell and developmental biology Medium 42170179
2018 Plau is a direct YAP/TEAD target gene in mouse skin keratinocytes; YAP2-5SA-ΔC overexpression upregulates Plau (with TEAD binding motifs in its 3' UTR), and Plau promotes keratinocyte proliferation in epidermal stem/progenitor cell populations. RNA-seq from YAP2-5SA-ΔC transgenic mouse skin, TEAD binding motif analysis, functional validation assays for proliferation Cell death & disease Low 30382077
2025 siRNA knockdown of PLAU decreased in vitro TNBC-endothelial cell interactions and ex vivo extravasation of MDA-MB231 mono-clusters, establishing a direct role for uPA/PLAU in breast cancer cell extravasation from capillary venules. siRNA knockdown, in vitro endothelial binding assay, ex vivo lung extravasation assay, single-cell RNA-seq bioRxivpreprint Low bio_10.1101_2025.06.11.659108
2025 OSBPL3 interacts with transcription factor NFE2L2, promoting its nuclear translocation and enhancing transcriptional activation of PLAU. PLAU upregulation then stimulates glycolytic enzyme expression through PI3K/AKT pathway activation, driving aerobic glycolysis and LUAD progression. Co-immunoprecipitation (OSBPL3-NFE2L2), nuclear fractionation, PLAU knockdown, AKT inhibition, metabolic assays (glucose consumption, lactate secretion), in vivo tumor models Translational oncology Medium 41687403
2025 PLAU activates Cox-2 expression in neuronal cells, leading to cellular senescence. Suppression of Plau in AD mice (via adeno-associated virus) reduced disease progression. Vilazodone, identified as a Plau inhibitor, triggers autophagy in senescent cells and eliminates them. AAV-mediated Plau knockdown in AD mice, cognitive function assays, Cox-2 pathway analysis, autophagy assays International immunopharmacology Low 40690806
2025 ZC3H13-mediated m6A modification increases PLAU mRNA stability and expression in oral squamous cell carcinoma; ZC3H13 overexpression rescued the suppressive effects of PLAU silencing on OSCC cells. MeRIP, RIP, mRNA stability assays, qRT-PCR, immunoblotting, rescue experiments Cytotechnology Medium 41377025
2025 In ESCC, EVA1A promotes glycolysis and lactate production; lactate drives histone H4K12 lactylation at the PLAU locus, enhancing PLAU expression. Elevated PLAU then suppresses CD8+ T cell anti-tumor activity. PLAU overexpression reversed CD8+ T cell activation induced by EVA1A silencing. Chromatin immunoprecipitation (ChIP) for H4K12la at PLAU locus, flow cytometry, qRT-PCR, ELISA, LDH assays, xenograft models, co-culture with CD8+ T cells Expert review of clinical immunology Medium 40826503

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression. Cell death & disease 93 25188512
2011 Inhibition of miR-193a expression by Max and RXRα activates K-Ras and PLAU to mediate distinct aspects of cellular transformation. Cancer research 75 21670079
2021 PLAU directs conversion of fibroblasts to inflammatory cancer-associated fibroblasts, promoting esophageal squamous cell carcinoma progression via uPAR/Akt/NF-κB/IL8 pathway. Cell death discovery 63 33574243
2009 Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood 63 20007542
2003 Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2. Neurogenetics 60 12898287
2019 MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression. Cancer management and research 55 31354344
2021 PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma. Frontiers in genetics 53 34093649
2019 Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor. Biotechnology and bioengineering 52 31317530
2020 FOXM1 functions collaboratively with PLAU to promote gastric cancer progression. Journal of Cancer 48 31949481
2012 PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells. Molecular systems biology 48 23169000
2022 Hyperglycemia Promotes Endothelial Cell Senescence through AQR/PLAU Signaling Axis. International journal of molecular sciences 45 35270021
2022 Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU). Frontiers in immunology 42 36591282
2014 Transcriptional complexity and roles of Fra-1/AP-1 at the uPA/Plau locus in aggressive breast cancer. Nucleic acids research 41 25200076
2020 Triptolide inhibits pancreatic cancer cell proliferation and migration via down-regulating PLAU based on network pharmacology of Tripterygium wilfordii Hook F. European journal of pharmacology 37 32464191
2008 Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes. Blood 37 18988861
2006 A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease. Human molecular genetics 36 16825285
2021 Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU). Cell death & disease 28 34244472
2018 Plau and Tgfbr3 are YAP-regulated genes that promote keratinocyte proliferation. Cell death & disease 27 30382077
2022 METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner. Biochemical and biophysical research communications 25 35567945
2022 PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer. Oncology reports 24 36524374
2024 Cuproptosis-related lncRNA JPX regulates malignant cell behavior and epithelial-immune interaction in head and neck squamous cell carcinoma via miR-193b-3p/PLAU axis. International journal of oral science 22 39511134
2021 Long non-coding RNA TRPM2-AS regulates microRNA miR-138-5p and PLAU (Plasminogen Activator, Urokinase) to promote the progression of gastric adenocarcinoma. Bioengineered 20 34696681
2010 Association of putative functional variants in the PLAU gene and the PLAUR gene with myocardial infarction. Clinical science (London, England : 1979) 19 20518747
2023 Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1. Acta pharmaceutica Sinica. B 17 38487008
2017 The duplication mutation of Quebec platelet disorder dysregulates PLAU, but not C10orf55, selectively increasing production of normal PLAU transcripts by megakaryocytes but not granulocytes. PloS one 17 28301587
2024 PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1. Biology direct 14 38229120
2022 Functional Validation of the Putative Oncogenic Activity of PLAU. Biomedicines 14 36672610
2023 MicroRNA-181b attenuates lipopolysaccharide-induced inflammatory responses in pulpitis via the PLAU/AKT/NF-κB axis. International immunopharmacology 13 38154211
2005 No association of a non-synonymous PLAU polymorphism with Alzheimer's disease and disease-related traits. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 13 15558716
2021 GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling. International journal of chronic obstructive pulmonary disease 12 34675506
2007 Association of tagSNPs in the urokinase-plasminogen activator (PLAU) gene with Alzheimer's disease and associated quantitative traits. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 12 16967469
2022 Proteomics analysis uncovers plasminogen activator PLAU as a target of the STING pathway for suppression of cancer cell migration and invasion. The Journal of biological chemistry 10 36496076
2023 PLAU contributes to the development of cholangiocarcinoma via activating NF-κB signaling pathway. Cell biology international 9 37067236
2006 The urokinase-type plasminogen activator polymorphism PLAU_1 is a risk factor for APOE-epsilon4 non-carriers in the Italian Alzheimer's disease population and does not affect the plasma Abeta(1-42) level. Neurobiology of disease 9 17174555
2022 Chrysin, which targets PLAU, protects PC12 cells from OGD/R-stimulated damage through repressing the NF-κB signaling pathway. Regenerative therapy 8 35097165
2015 Epileptogenesis after traumatic brain injury in Plau-deficient mice. Epilepsy & behavior : E&B 8 26253597
2014 Effect of hypoxia on the expression of CCN2, PLAU, PLAUR, SLURP1, PLAT and ITGB1 genes in ERN1 knockdown U87 glioma cells. Ukrainian biochemical journal 8 25509186
2023 m6A Methyltransferase, WTAP, Promotes Cancer Progression in Laryngeal Squamous Cell Carcinoma by Regulating PLAU Stability. Annals of clinical and laboratory science 7 37094860
2020 Plau/Plaur double-deficiency did not worsen lesion severity or vascular integrity after traumatic brain injury. Neuroscience letters 7 32360936
2025 Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis by inhibiting hepatocyte ferroptosis and macrophage polarization via the miR-455-3p/PLAU axis. Stem cell research & therapy 6 40739265
2024 PLAU promotes cell proliferation and migration of head and neck cancer via STAT3 signaling pathway. Experimental cell research 6 38663475
2024 PLAU, transcriptionally negatively regulated by GATA6, promotes lung squamous carcinoma cell proliferation and migration. Biochimica et biophysica acta. Molecular cell research 6 38702016
2021 Identification of de novo EP300 and PLAU variants in a patient with Rubinstein-Taybi syndrome-related arterial vasculopathy and skeletal anomaly. Scientific reports 6 34354133
2014 The PLAU P141L single nucleotide polymorphism is associated with collateral circulation in patients with coronary artery disease. Revista espanola de cardiologia (English ed.) 6 24952395
2025 Single-cell transcriptomics reveals hypoxia-driven iCAF_PLAU is associated with stemness and immunosuppression in anorectal malignant melanoma. Journal of gastroenterology 5 40613916
2025 Hypoxia-induced tumor cell-intrinsic PLAU activation drives immunotherapy resistance in collagenic lung adenocarcinoma. International immunopharmacology 4 40639051
2021 Two Rare Variants in PLAU and BACE1 Genes-Do They Contribute to Semantic Dementia Clinical Phenotype? Genes 4 34828412
2025 Huafengdan Inhibits Glioblastoma Cell Growth and Mobility by Acting on PLAU and CAV1 Targets. Pharmaceuticals (Basel, Switzerland) 2 40143204
2025 Roles of MARCKSL1, MCM6, RFC4, and PLAU genes in esophageal cancer and their association with radiotherapy response. Scientific reports 2 40603489
2025 Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer. Cancer cell international 2 40646496
2025 Plasma apolipoprotein E protein attenuates pulmonary fibrosis through LRP1 and PLAU dual receptor-mediated TGF-β/Smad inhibition. Journal of advanced research 2 41475664
2025 Vilazodone ameliorates senescence-related Alzheimer's disease like symptoms by targeting Plau to induce autophagy in senescent cells. International immunopharmacology 1 40690806
2025 EVA1A facilitates glycolysis in esophageal squamous cell carcinoma to boost PLAU histone lactylation and dampen CD8+ T cell activity. Expert review of clinical immunology 1 40826503
2025 Exosomal FOSL1 From Cancer-associated Fibroblasts Drives the Progression and Pro-tumorigenic M2 Macrophage Polarization of Hepatocellular Carcinoma By Activating PLAU Transcription. Applied biochemistry and biotechnology 1 41264215
2011 Cloning of the 5' regulatory regions and functional characterization of the core promoters of ovine PLAU (u-PA) and SERPIN1 (PAI-1). Gene 1 21914465
2026 Integrated Transcriptomics and Experimental Validation Reveal That Ellagic Acid Alleviates Fuchs Endothelial Corneal Dystrophy via PLAU/NF-κB Signaling. Investigative ophthalmology & visual science 0 41532702
2026 OSBPL3 promotes LUAD metastasis and glycolysis through transcriptional upregulation of PLAU via NFE2L2. Translational oncology 0 41687403
2026 Downregulated PLAU alleviates acute rejection after liver transplantation by targeting Ptgs2 in macrophages. Frontiers in immunology 0 41988206
2026 Lactate-associated gene PLAU promotes liver metastasis of pancreatic ductal adenocarcinoma. Computational biology and chemistry 0 42048949
2026 Genetic Basis of Atherosclerosis: The Role of PLAU Gene Polymorphism in Coronary Artery Disease. Genetic testing and molecular biomarkers 0 42059534
2026 Novel mouse line with D277N mutation in the Plau gene displays autism spectrum disorder-like traits. Frontiers in cell and developmental biology 0 42170179
2025 Correction: Lin et al. Huafengdan Inhibits Glioblastoma Cell Growth and Mobility by Acting on PLAU and CAV1 Targets. Pharmaceuticals 2025, 18, 428. Pharmaceuticals (Basel, Switzerland) 0 40573327
2025 Nucleus pulposus cell-associated PLAU promotes intervertebral disc degeneration through HIPPO pathway. Pathology, research and practice 0 40700932
2025 TGF-β1 Up-Regulates PLAU Expression to Promote Invasion and Migration of Oral Squamous Cell Carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 0 41285165
2025 PLAU regulated by a m6A writer ZC3H13 plays the oncogenic role in oral squamous cell carcinoma. Cytotechnology 0 41377025
2025 Upregulation of PLAU in granulosa cells disrupts steroid hormone synthesis and promotes apoptosis by activating NF-κB signaling pathway in PCOS. Journal of ovarian research 0 41462288
2025 Identification of COL3A1, PLAU, and SPP1 as Key Biomarkers for Early Detection of Esophageal Cancer. International journal of molecular sciences 0 41465316

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