ArticleJournal of experimental & clinical cancer research : CR2023
Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- QRICH1 Suppresses Glioma Progression by Inducing ER Stress and Activating the PERK-ATF4-CHOP Pathway.Cancer medicine · 2026Article
- Circulating PDIA4, MMP-2, MMP-9, and Claudin-2 in Vitamin D-Deficient Patients with Brain Tumors: An Exploratory Clinical Pilot Study.Journal of clinical medicine · 2026Article
- Regulatory Mechanisms of XBP1 in Tumorigenesis and Cancer Progression: Challenges and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tetrastigma Hemsleyanum Polysaccharide Suppresses Triple-Negative Breast Cancer by Disrupting the Hippo-YAP/TEAD4-PDIA4 Axis and Endoplasmic Reticulum Stress Adaptation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NAT10-mediated ac4C modifications regulate glioblastoma progression.Cell death & disease · 2026Article
- DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis.Cell death & disease · 2025Article
- Prognostic Factors and Talaporfin Sodium Concentration in Photodynamic Therapy for Recurrent Grade 4 Glioma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Thioredoxin related transmembrane protein 1acts as a prognostic indictor and promotes proliferation and TMZ resistance of lower-grade glioma.Scientific reports · 2025Article
- ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma.Scientific reports · 2024Article
- Article
- The future of cancer therapy: exploring the potential of patient-derived organoids in drug development.Frontiers in cell and developmental biology · 2024Review
- RUNX1-PDIA5 Axis Promotes Malignant Progression of Glioblastoma by Regulating CCAR1 Protein Expression.International journal of biological sciences · 2024Article
- Article
- The role of angiogenic growth factors in the immune microenvironment of glioma.Frontiers in oncology · 2023Review
- LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17.The breast journal · 2023Article
- ERP44 Is Associated With Poor Prognosis and Promotes Proliferation and Temozolomide Resistance in Lower-grade Glioma.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
introductionIncreasing evidence has revealed the key activity of protein disulfide isomerase A4 (PDIA4) in the endoplasmic reticulum stress (ERS) response. However, the role of PDIA4 in regulating glioblastoma (GBM)-specific pro-angiogenesis is still unknown.
methodsThe expression and prognostic role of PDIA4 were analyzed using a bioinformatics approach and were validated in 32 clinical samples and follow-up data. RNA-sequencing was used to search for PDIA4-associated biological processes in GBM cells, and proteomic mass spectrum (MS) analysis was used to screen for potential PDIA4 substrates. Western blotting, real-time quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assays (ELISA) were used to measure the levels of the involved factors. Cell migration and tube formation assays determined the pro-angiogenesis activity of PDIA4 in vitro. An intracranial U87 xenograft GBM animal model was constructed to evaluate the pro-angiogenesis role of PDIA4 in vivo.
resultsAberrant overexpression of PDIA4 was associated with a poor prognosis in patients with GBM, although PDIA4 could also functionally regulate intrinsic GBM secretion of vascular endothelial growth factor-A (VEGF-A) through its active domains of Cys-X-X-Cys (CXXC) oxidoreductase. Functionally, PDIA4 exhibits pro-angiogenesis activity both in vitro and in vivo, and can be upregulated by ERS through transcriptional regulation of X-box binding protein 1 (XBP1). The XBP1/PDIA4/VEGFA axis partially supports the mechanism underlying GBM cell survival under ER stress. Further, GBM cells with higher expression of PDIA4 showed resistance to antiangiogenic therapy in vivo.
conclusionsOur findings revealed the pro-angiogenesis role of PDIA4 in GBM progression and its potential impact on GBM survival under a harsh microenvironment. Targeting PDIA4 might help to improve the efficacy of antiangiogenic therapy in patients with GBM.
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