ArticleScientific reports2021
Activating transcription factor 4 mediates adaptation of human glioblastoma cells to hypoxia and temozolomide.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- The p53-Associated Regulation of ATF4 mRNA Expression Involves p21 and p130 in a Stress-Dependent Manner.Cells · 2026Article
- Article
- Targeting glioblastoma mitochondrial metabolism with S-Gboxin induces cytotoxicity under conditions of the tumor microenvironment.Cell death discovery · 2026Article
- The Janus framework of the integrated stress response: from homeostasis to maladaptation.Life science alliance · 2026Review
- Integrated Bioinformatics and Experimental Validation Reveal Fuzheng Yi'ai Formula Induces Immunogenic Cell Death Via the PERK-eIF2α-ATF4 Pathway for Prostate Cancer Treatment.Biological procedures online · 2026Article
- Glioma‑associated microglia and macrophages as a potential target for mTOR inhibition in glioblastoma.Molecular medicine reports · 2025Article
- TMEM166 negatively regulates unfolded protein response to affect hepatocellular carcinoma cell growth and sorafenib resistance.Cell death & disease · 2025Article
- Review
- Development of Stimuli-Responsive Polymeric Nanomedicines in Hypoxic Tumors and Their Therapeutic Promise in Oral Cancer.Polymers · 2025Review
- Adaptation mechanisms in cancer: Lipid metabolism under hypoxia and nutrient deprivation as a target for novel therapeutic strategies (Review).Molecular medicine reports · 2025Review
- AMP-activated protein kinase mediates adaptation of glioblastoma cells to conditions of the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Article
- Impaired RelA signaling and lipid metabolism dysregulation in hepatocytes: driving forces in the progression of metabolic dysfunction-associated steatotic liver disease.Cell death discovery · 2025Article
- Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations.Current medicinal chemistry · 2025Review
- Superoxide dismutase 1 mediates adaptation to the tumor microenvironment of glioma cells via mammalian target of rapamycin complex 1.Cell death discovery · 2024Article
- Triggering of endoplasmic reticulum stress via ATF4-SPHK1 signaling promotes glioblastoma invasion and chemoresistance.Cell death & disease · 2024Article
- Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.Science advances · 2024Article
- Translational modulator ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome.iScience · 2024Article
- The PERK Branch of the Unfolded Protein Response Safeguards Protein Homeostasis and Mesendoderm Specification of Human Pluripotent Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.Science advances · 2023Review
- Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?Biomedicines · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrated stress response (ISR) is a central cellular adaptive program that is activated by diverse stressors including ER stress, hypoxia and nutrient deprivation to orchestrate responses via activating transcription factor 4 (ATF4). We hypothesized that ATF4 is essential for the adaptation of human glioblastoma (GB) cells to the conditions of the tumor microenvironment and is contributing to therapy resistance against chemotherapy. ATF4 induction in GB cells was modulated pharmacologically and genetically and investigated in the context of temozolomide treatment as well as glucose and oxygen deprivation. The relevance of the ISR was analyzed by cell death and metabolic measurements under conditions to approximate aspects of the GB microenvironment. ATF4 protein levels were induced by temozolomide treatment. In line, ATF4 gene suppressed GB cells (ATF4sh) displayed increased cell death and decreased survival after temozolomide treatment. Similar results were observed after treatment with the ISR inhibitor ISRIB. ATF4sh and ISRIB treated GB cells were sensitized to hypoxia-induced cell death. Our experimental study provides evidence for an important role of ATF4 for the adaptation of human GB cells to conditions of the tumor microenvironment characterized by low oxygen and nutrient availability and for the development of temozolomide resistance. Inhibiting the ISR in GB cells could therefore be a promising therapeutic approach.
Indexed as
Identifiers
What OpenQuestion holds
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.