ArticleJournal of the National Cancer Institute2020
Role of Asparagine Endopeptidase in Mediating Wild-Type p53 Inactivation of Glioblastoma.
Article in Journal of the National Cancer Institute, 2020. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Chemotherapeutic drug-triggered AEP-cleaved G3BP1 orchestrates stress granules/nucleoli/mitochondria in osteosarcoma.Bone research · 2025Article
- Targeting PGE2 mediated senescent neuron improves tumor therapy.Neuro-oncology · 2025Article
- Targeting legumain-mediated cell-cell interaction sensitizes glioblastoma to immunotherapy in preclinical models.The Journal of clinical investigation · 2025Article
- ANG-Modified Liposomes Coloaded With α-Melittin and Resveratrol Induce Apoptosis and Pyroptosis in Glioblastoma Cells by Impeding Wnt/β-Catenin Signaling.CNS neuroscience & therapeutics · 2025Article
- Structural and mechanistic diversity in p53-mediated regulation of organismal longevity across taxonomical orders.PLoS computational biology · 2025Article
- Intranasal delivery of AEP inhibitor-loaded neuron-targeted liposome ameliorates radiation-induced brain injury.Materials today. Bio · 2025Article
- Radiotherapy resistance driven by Asparagine endopeptidase through ATR pathway modulation in breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Associations of Serum Legumain with Severity and Prognosis Among Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients.International journal of chronic obstructive pulmonary disease · 2025Article
- scParser: sparse representation learning for scalable single-cell RNA sequencing data analysis.Genome biology · 2024Article
- Unlocking the Gateway: The Spatio-Temporal Dynamics of the p53 Family Driven by the Nuclear Pores and Its Implication for the Therapeutic Approach in Cancer.International journal of molecular sciences · 2024Review
- Asparagine endopeptidase deficiency mitigates radiation-induced brain injury by suppressing microglia-mediated neuronal senescence.iScience · 2024Article
- AEP promotes aberrant RNA splicing through DDX3X cleavage in solid tumors.The Journal of clinical investigation · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- AEP-cleaved DDX3X induces alternative RNA splicing events to mediate cancer cell adaptation in harsh microenvironments.The Journal of clinical investigation · 2023Article
- Asparaginyl endopeptidase contributes to cetuximab resistance via MEK/ERK signaling in RAS wide-type metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Role of LGMN in tumor development and its progression and connection with the tumor microenvironment.Frontiers in molecular biosciences · 2023Review
- The Mammalian Cysteine Protease Legumain in Health and Disease.International journal of molecular sciences · 2022Review
- Super-resolution of brain tumor MRI images based on deep learning.Journal of applied clinical medical physics · 2022Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIsocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood.
methodsWe investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests.
resultsWe demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery.
conclusionsOur results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM.
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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.