ArticleOncoimmunology2021
IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells.
Article in Oncoimmunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Global research and emerging trends in autophagy in lung cancer: a bibliometric and visualized study from 2013 to 2022.Frontiers in pharmacology · 2024Pooled it
- Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.International journal of molecular sciences · 2021Pooled it
- The adhesion G protein-coupled receptor F5 is a crucial regulator of CD4Genes & diseases · 2027Article
- Histone H4 lysine 20 tri-methylation safeguards breast cancer lineage fidelity and unfolded protein response.Nature communications · 2026Article
- Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid-Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling.Neurochemical research · 2026Article
- Targeting endoplasmic reticulum export disrupts metabolic resilience in multiple myeloma.Signal transduction and targeted therapy · 2026Article
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- Gambogic acid induces cell death via covalent binding with PRDX1 to regulate ER stress and autophagy.Chinese medicine · 2026Article
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Inflammatory cytokines induce new cancer dependencies.Nature genetics · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Uncovering a new player in ischemic stroke: a study of intra-arterial interferon-gamma-producing CD14Journal of neuroinflammation · 2026Article
- Dual-function cytokines as modulators of autophagy: reprogramming inflammatory resolution in severe COVID-19.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- KDM5B recruits FOXG1 to suppress the IFN response, leading to malignant progression and immune evasion in cervical cancer.Frontiers in medicine · 2026Article
- AUDA suppresses apoptosis of HCAECs induced by TNF and serum of Kawasaki disease patients by inhibiting endoplasmic reticulum stress.Open life sciences · 2026Article
- An E3 Aptamer-Modified T Cell-Derived Exosomal Nanoplatform for Codelivery of Astragaloside IV and PESV: Enhancing Prostate Cancer Therapy Through Immune Modulation with Implications for Clinical Translation.International journal of nanomedicine · 2026Article
- A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse.Protein & cell · 2026Article
- IFNγ-induced antigen loss in chimeric antigen receptor-T cell therapy.Frontiers in immunology · 2026Article
- LDHA, BIK, and CNIH4 Are Diagnostic Markers of Endoplasmic Reticulum Stress in Lung Cancer Comorbid With Sepsis: Integrating Machine Learning and Single-Cell Analysis of Immune Signaling.Mediators of inflammation · 2026Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-gamma (IFN-γ) is a major effector molecule of immunity and a common feature of tumors responding to immunotherapy. Active IFN-γ signaling can directly trigger apoptosis and cell cycle arrest in human cancer cells. However, the mechanisms underlying these actions remain unclear. Here, we report that IFN-γ rapidly increases protein synthesis and causes the unfolded protein response (UPR), as evidenced by the increased expression of glucose-regulated protein 78, activating transcription factor-4, and c/EBP homologous protein (CHOP) in cells treated with IFN-γ. The JAK1/2-STAT1 and AKT-mTOR signaling pathways are required for IFN-γ-induced UPR. Endoplasmic reticulum (ER) stress promotes autophagy and restores homeostasis. Surprisingly, in IFN-γ-treated cells, autophagy was impaired at the step of autophagosome-lysosomal fusion and caused by a significant decline in the expression of lysosomal membrane protein-1 and -2 (LAMP-1/LAMP-2). The ER stress inhibitor 4-PBA restored LAMP expression in IFN-γ-treated cells. IFN-γ stimulation activated the protein kinase-like ER kinase (PERK)-eukaryotic initiation factor 2a subunit (eIF2α) axis and caused a reduction in global protein synthesis. The PERK inhibitor, GSK2606414, partially restored global protein synthesis and LAMP expression in cells treated with IFN-γ. We further investigated the functional consequences of IFN-γ-induced ER stress. We show that inhibition of ER stress significantly prevents IFN-γ-triggered apoptosis. CHOP knockdown abrogated IFN-γ-mediated apoptosis. Inhibition of ER stress also restored cyclin D1 expression in IFN-γ-treated cells. Thus, ER stress and the UPR caused by IFN-γ represent novel mechanisms underlying IFN-γ-mediated anticancer effects. This study expands our understanding of IFN-γ-mediated signaling and its cellular actions in tumor cells.
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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.