ArticleBritish journal of cancer2019
The physiological mTOR complex 1 inhibitor DDIT4 mediates therapy resistance in glioblastoma.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 77 citations in OpenAlex.
- Anti-myeloma mechanisms of the selective NF-κB inhibitor QNZ.Molecular therapy. Oncology · 2026Article
- Enhancer-mediated DDIT4 activation by SMYD2-dependent H3K4me1 promotes pazopanib resistance in clear cell renal cell carcinoma.Journal of translational medicine · 2026Article
- Article
- Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.Cell communication and signaling : CCS · 2026Article
- Apoptosis-related gene model predicts the prognosis in patients with acute myeloid leukemia.Blood science (Baltimore, Md.) · 2026Article
- Identification of hsa-miR-144-3p as a novel immunotherapeutic target for glioblastoma based on disulfidptosis-related analysis.Discover oncology · 2026Article
- DNA topological regulation by topoisomerase IIβ-DNA-PK interaction is important for controlled hypoxia-inducible gene expression.bioRxiv : the preprint server for biology · 2026Article
- Electrolyzed Hydrogen Water Improves Chemosensitivity to Anticancer Drugs by Potently Suppressing Autophagy.Journal of cellular and molecular medicine · 2026Article
- SIX2-Mediated Microglial M2 Polarization and Exosomal miR-3470b Delivery Protect Dopaminergic Neurons in Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Nomilin Rewires mTOR-Driven Immunometabolism via DDIT4 to Restrain Psoriasis.International journal of biological sciences · 2026Article
- Pan-cancer gene set discovery via scRNA-seq for optimal deep learning based downstream tasks.Scientific reports · 2025Article
- Age-related microbiome metabolites alter RNA splicing and chromatin accessibility in the brain.bioRxiv : the preprint server for biology · 2025Article
- The critical role of DNA damage-inducible transcript 4 (DDIT4) in stemness character of leukemia cells and leukemia initiation.Molecular oncology · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Metformin suppresses the mitochondrial and transcriptional response to exercise, revealing a conserved BCL6B-associated angiogenic program.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Article
- Establishment of a prognostic model based on ER stress-related cell death genes and proposing a novel combination therapy in acute myeloid leukemia.Journal of translational medicine · 2025Article
- TFE3 fusion oncoprotein condensates drive transcriptional reprogramming and cancer progression in translocation renal cell carcinoma.Cell reports · 2025Article
- Lower cytoplasmic expression of DDIT4 is associated with poor prognosis in gastric cancer patients.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite significant advances in the understanding of glioblastoma genetics and biology, survival is still poor. Hypoxia and nutrient depletion in the tumour microenvironment induce adaptive signalling and metabolic responses, which can influence sensitivity to therapeutic regimens. DNA damage-inducible transcript 4 (DDIT4) is a protein induced by hypoxia and in response to DNA stress. Mechanistically, DDIT4 inhibits mammalian target of rapamycin complex 1 (mTORC1) signalling by activation of the tuberous sclerosis 1/2 (TSC1/2) complex.
methodsUsing short hairpin RNA-mediated gene suppression as well as doxycycline-regulated gene induction, we developed a glioblastoma cell model to study effects of DDIT4 under conditions of the glioblastoma microenvironment and therapy.
resultsWe found an intact DDIT4-mTORC1 signalling axis in human glioblastoma cells that was inducible by hypoxia. Temozolomide and radiotherapy also induced DDIT4 and repressed mTORC1 activity in some glioblastoma cell lines. DDIT4 gene suppression sensitised glioma cells towards hypoxia-induced cell death, while DDIT4 overexpression protected them. Additionally, in clonogenic survival analyses, DDIT4 induction conferred protection from radiotherapy and temozolomide, while DDIT4 gene suppression sensitised cells.
conclusionsWe identified DDIT4 as a cell-intrinsic regulator for adaptive responses and therapy resistance in glioblastoma cells which may interfere with cell death induction by temozolomide, radiotherapy or hypoxia by inhibiting mTORC1 activity.
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