ArticleOncogene2013
Endoplasmic reticulum stress triggers autophagy in malignant glioma cells undergoing cyclosporine a-induced cell death.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- SRSF3 promotes the generation of XBP1s to stabilize autophagy and enhance hypoxia adaptation in glioma.European journal of histochemistry : EJH · 2026Article
- Cyclosporine A Ameliorates Inflammatory Responses in Dry Eye by Inactivating cGAS-STING Signaling Via the Initiation of Autophagy.Investigative ophthalmology & visual science · 2025Article
- Shared and non-overlapping functions of RECQL4 and BLM helicases in chemotherapeutics-induced glioma cell responses.BMC cancer · 2025Article
- N-palmitoyl glycine mediates depression-associated atrial fibrillation via Man1a2-dependent autophagy and NRAP dysregulation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Autophagy initiation triggers p150Cellular and molecular life sciences : CMLS · 2024Article
- Targeting the Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment as a Potential Anti-Cancer Strategy.International journal of molecular sciences · 2024Review
- The antitumor action of endocannabinoids in the tumor microenvironment of glioblastoma.Frontiers in pharmacology · 2024Review
- SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop.Journal of experimental & clinical cancer research : CR · 2023Article
- Differential dose-response effect of cyclosporine A in regulating apoptosis and autophagy markers in MCF-7 cells.Inflammopharmacology · 2023Article
- Dual role of endoplasmic reticulum stress-ATF-6 activation in autophagy and apoptosis induced by cyclic stretch in myoblast.Apoptosis : an international journal on programmed cell death · 2023Article
- BLM helicase overexpressed in human gliomas contributes to diverse responses of human glioma cells to chemotherapy.Cell death discovery · 2023Article
- Article
- Identification of an endoplasmic reticulum stress-related signature associated with clinical prognosis and immune therapy in glioma.BMC neurology · 2022Article
- The Molecular Quality and Mitochondrial Activity of Porcine Cumulus-Oocyte Complexes Are Affected by Their Exposure to Three Endocrine-Active Compounds under 3D In Vitro Maturation Conditions.International journal of molecular sciences · 2022Article
- Vacuolar proteases and autophagy in phytopathogenic fungi: A review.Frontiers in fungal biology · 2022Review
- An Overview of Autophagy in Hematopoietic Stem Cell Transplantation.Frontiers in bioengineering and biotechnology · 2022Review
- Tamoxifen Sensitizes Acute Lymphoblastic Leukemia Cells to Cannabidiol by Targeting Cyclophilin-D and Altering Mitochondrial CaInternational journal of molecular sciences · 2021Article
- Apatinib induces endoplasmic reticulum stress-mediated apoptosis and autophagy and potentiates cell sensitivity to paclitaxel via the IRE-1α-AKT-mTOR pathway in esophageal squamous cell carcinoma.Cell & bioscience · 2021Article
- Autophagy and Digestive Disorders: Advances in Understanding and Therapeutic Approaches.Biomolecules & therapeutics · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a conserved, self-digestion process that is activated in response to nutrient limitation but acting also as an alternative death mechanism under certain conditions. It is accompanied by the progressive formation of vesicle structures from autophagosomes to autophagolysosomes orchestrated by autophagy effectors (Atg proteins) and modulators (that is, mTOR-mammalian target of rapamycin as a negative regulator). Malignant gliomas are highly resistant to current therapies that induce apoptosis, thus induction of the alternative cell death is an attractive strategy. We demonstrate that cyclosporine A (CsA, an immunophilin/calcineurin inhibitor) induces cell death with some apoptotic features but also accompanied by the appearance of numerous cytoplasmic vacuoles, immunostained for endoplasmic reticulum (ER) and autophagy markers. The induction of ER stress in glioma cells by CsA was evidenced by detection of unfolded protein response activation (phosphorylation of PERK, accumulation of IRE1α) and accumulation of ER stress-associated proteins (BIP and CHOP). Formation of the acidic vesicular organelles, increase of autophagic vacuoles, GFP-LC3 punctation (microtubule-associated protein light chain 3) and LC3-II accumulation upon CsA treatment confirmed activation of autophagy. Decrease of phosphorylation of 4E-BP1, p70S6K1 and its downstream target S6 ribosomal protein demonstrate inhibition of mTOR signaling by CsA. Salubrinal and silencing of PERK and IRE1α partially blocked CsA-induced accumulation of LC3-II. It suggests that ER stress precedes CsA-induced autophagy. Surprisingly, silencing of autophagy effectors ULK1, Atg5 or Atg7 increased the level of active caspases 3, 7 and PARP degradation in CsA-treated cells. Our results demonstrate that CsA induces both apoptosis and autophagy in malignant glioma cells via induction of ER stress and inhibition of mTOR/p70S6K1 pathway, however autophagy is cytoprotective in this context.
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Registered trials
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.