ArticleJournal of experimental & clinical cancer research : CR2021
Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Stanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis.Oncogenesis · 2026Article
- p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma.Nature communications · 2026Article
- Article
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma.Scientific reports · 2025Article
- Impaired microglial glycolysis promotes inflammatory responses after intracerebral haemorrhage via HK2-dependent mitochondrial dysfunction.Journal of advanced research · 2025Article
- ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.Journal of molecular cell biology · 2025Article
- Review
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Glioma-Associated Mesenchymal Stromal/Stem Cells Derived Exosomal miR-191 Promotes the Proneural-to-Mesenchymal Transition in Glioblastoma Cells via PTEN/PI3K/AKT Signaling.International journal of nanomedicine · 2025Article
- CCN1 Promotes Mesenchymal Phenotype Transition Through Activating NF-κB Signaling Pathway Regulated by S100A8 in Glioma Stem Cells.CNS neuroscience & therapeutics · 2024Article
- Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma.Cancers · 2024Article
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
- Cell-Surface GRP78-Targeted Chimeric Antigen Receptor T Cells Eliminate Lung Cancer Tumor Xenografts.International journal of molecular sciences · 2024Article
- Chimeric antigen receptor T cells targeting cell surface GRP78 efficiently kill glioblastoma and cancer stem cells.Journal of translational medicine · 2023Article
- Insulin-like growth factor binding protein-2 and glucose-regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH-wildtype glioblastoma patients.Cancer medicine · 2023Article
- The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma.International journal of molecular sciences · 2023Review
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- SPI1-mediated MIR222HG transcription promotes proneural-to-mesenchymal transition of glioma stem cells and immunosuppressive polarization of macrophages.Theranostics · 2023Article
- The anterior gradient homologue 2 (AGR2) co-localises with the glucose-regulated protein 78 (GRP78) in cancer stem cells, and is critical for the survival and drug resistance of recurrent glioblastoma: in situ and in vitro analyses.Cancer cell international · 2022Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlioma stem cells (GSCs) are considered the initial cells of gliomas, contributing to therapeutic resistance. Patient-derived GSCs well recapitulate the heterogeneity of their parent glioma tissues, which can be classified into different subtypes. Likewise, previous works identified GSCs as two distinct subtypes, mesenchymal (MES) and proneural (PN) subtypes, and with general recognition, the MES subtype is considered a more malignant phenotype characterized by high invasion and radioresistance. Therefore, understanding the mechanisms involved in the MES phenotype is necessary for glioblastoma treatment.
methodsData for bioinformatic analysis were obtained from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database. An antibody was used to block cell surface glucose-regulated protein 78 (csGRP78). Apoptosis and cell cycle analyses were performed to evaluate radiation damage. Immunofluorescence staining was applied to assess protein expression and distribution. Mass spectrometry combined with bioinformatic analysis was used to screen downstream molecules. Intracranial GSC-derived xenografts were established for in vivo experiments.
resultsTotal GRP78 expression was associated with MES GSC stemness, and csGRP78 was highly expressed in MES GSCs. Targeting csGRP78 suppressed the self-renewal and radioresistance of MES GSCs in vitro and in vivo, accompanied by downregulation of the STAT3, NF-κB and C/EBPβ pathways. Mass spectrometry revealed the potential downstream β-site APP-cleaving enzyme 2 (BACE2), which was regulated by csGRP78 via lysosomal degradation. Knockdown of BACE2 inactivated NF-κB and C/EBPβ and significantly suppressed the tumorigenesis and radioresistance of MES GSCs in vitro and in vivo.
conclusionsCell surface GRP78 was preferentially expressed in MES GSCs and played a pivotal role in MES phenotype maintenance. Thus, blocking csGRP78 in MES GSCs with a high-specificity antibody might be a promising novel therapeutic strategy.
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