ArticleCell death & disease2014
Plasminogen activator urokinase expression reveals TRAIL responsiveness and supports fractional survival of cancer cells.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
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- Profibrinolytic Factors and Cancer Progression, Metastasis, and Survival.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
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- Thymidine phosphorylase facilitates retinoic acid inducible gene-I induced endothelial dysfunction.Cell death & disease · 2023Article
- BdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity.Nature communications · 2023Article
- Functional Validation of the Putative Oncogenic Activity ofBiomedicines · 2022Article
- Review
- 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 · 2021Article
- Improved therapeutic efficacy of quercetin-loaded polymeric nanoparticles on triple-negative breast cancer by inhibiting uPA.RSC advances · 2020Article
- Apoptosis and genes involved in oral cancer - a comprehensive review.Oncology reviews · 2020Article
- TRAIL-induced variation of cell signaling states provides nonheritable resistance to apoptosis.Life science alliance · 2019Article
- SerpinB2 inhibits migration and promotes a resolution phase signature in large peritoneal macrophages.Scientific reports · 2019Article
- Asymmetric Inheritance of Cell Fate Determinants: Focus on RNA.Non-coding RNA · 2019Review
- Article
- MicroRNA-645 targets urokinase plasminogen activator and decreases the invasive growth of MDA-MB-231 triple-negative breast cancer cells.OncoTargets and therapy · 2018Article
- Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells.Cell death & disease · 2017Article
- Urokinase plasminogen activator protects cardiac myocytes from oxidative damage and apoptosis via hOGG1 induction.Apoptosis : an international journal on programmed cell death · 2017Article
- Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis.Genome medicine · 2016Article
- BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10/Apo2L) holds promise for cancer therapy as it induces apoptosis in a large variety of cancer cells while exerting negligible toxicity in normal ones. However, TRAIL can also induce proliferative and migratory signaling in cancer cells resistant to apoptosis induced by this cytokine. In that regard, the molecular mechanisms underlying the tumor selectivity of TRAIL and those balancing apoptosis versus survival remain largely elusive. We show here that high mRNA levels of PLAU, which encodes urokinase plasminogen activator (uPA), are characteristic of cancer cells with functional TRAIL signaling. Notably, decreasing uPA levels sensitized cancer cells to TRAIL, leading to markedly increased apoptosis. Mechanistic analyses revealed three molecular events taking place in uPA-depleted cells: reduced basal ERK1/2 prosurvival signaling, decreased preligand decoy receptor 2 (DcR2)-death receptor 5 (DR5) interaction and attenuated recruitment of DcR2 to the death-inducing signaling complex upon TRAIL challenge. These phenomena were accompanied by increased FADD and procaspase-8 recruitment and processing, thus guiding cells toward a caspase-dependent cell death that is largely independent of the intrinsic apoptosis pathway. Collectively, our results unveil PLAU mRNA levels as marker for the identification of TRAIL-responsive tumor cells and highlight a key role of uPA signaling in 'apoptosis versus survival' decision-making processes upon TRAIL challenge.
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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.