ArticleCellular & molecular biology letters2021
Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling.
Article in Cellular & molecular biology letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 1 of them a synthesis that pooled it.
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Who cites it
180 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.
- Review of ferroptosis in colorectal cancer: Friends or foes?World journal of gastroenterology · 2023Pooled it
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Metformin Inhibits Ferroptotic Cell Death by Suppressing Cysteine Deprivation-Induced Mitochondrial Dysfunction.Pharmacology research & perspectives · 2026Article
- Lapatinib suppresses cysteine deprivation-induced ferroptotic cell death by modulating mitochondrial function.Medical oncology (Northwood, London, England) · 2026Article
- The Emerging Role of Ferroptosis in Pediatric Cancer Biology and Therapy.International journal of molecular sciences · 2026Review
- Targeting ferroptosis to overcome drug resistance in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Inhibition of DLX6 sensitizes lung adenocarcinoma to cisplatin via GPX4-dependent ferroptosis.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- GLI2 confers ferroptosis resistance in bladder cancer by transcriptionally upregulating PRDX1.Apoptosis : an international journal on programmed cell death · 2026Article
- Lipid Metabolism, Lipogenesis, and Resistance to Third Generation EGFR-TKIs.Journal of clinical laboratory analysis · 2026Review
- DLL1-mediated ferroptosis resistance via the Notch-Nrf2/GPX4 axis drives cisplatin resistance in ovarian cancer.Cancer & metabolism · 2026Article
- Targeting Cuproptosis and Ferroptosis via a ROS-Responsive Nanoplatform for Enhanced Synergistic Therapy Against Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2026Article
- Machine learning identifies key cells and therapeutic targets during ferroptosis after spinal cord injury.Neural regeneration research · 2026Article
- Ferroptosis-based therapeutic strategy targeting iron metabolism and SLC7A11 overcomes oxaliplatin resistance in patient-derived pancreatic cancer organoids.Journal of experimental & clinical cancer research : CR · 2026Article
- Multi-algorithm machine learning combined with in silico gene knockout reveals the diagnostic value and functional regulatory networks of ferroptosis-related genes in gastric cancer.Translational cancer research · 2026Article
- Platycodin D Overcomes Cisplatin Resistance in Gastric Cancer by Inducing Ferroptosis through TLK1-Dependent UHRF2/DNMT3A/ALOX15 Pathway.Chinese journal of integrative medicine · 2026Article
- Bufalin Suppresses Pancreatic Ductal Adenocarcinoma Through ER Stress-Ferroptosis Crosstalk Associated with IPInternational journal of molecular sciences · 2026Article
- Review
- AURKA suppresses NCOA4-mediated ferritinophagy to enhance sorafenib resistance in hepatocellular carcinoma.Cell death & disease · 2026Article
- Targeting the ODC1-YBX1 axis reverses gastric cancer chemoresistance via transcriptional control of SLC7A11-mediated ferroptosis.Cell death discovery · 2026Article
120 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrently, resistance against cisplatin (DDP) is a frequent problem for the success of advanced gastric carcinoma (GC) chemotherapy. Here, we sought to investigate the function of activating transcription factor 3 (ATF3) n GC chemoresistance.
methodsExpression of ATF3 was determined in GC cell lines (MNK45, SGC7901, and BGC823) and cisplatin (DDP)-resistant cells (SGC7901/DDP and BGC823/DDP). Biological informatics was performed to analyze ATF3 expression and prognosis in GC patients. Cisplatin resistance was evaluated. Ferroptosis was detected after ATF3 transfection of cells. The underlying molecular mechanism was also investigated.
resultsTranscripts of ATF3 were decreased in GC cells and GC tissues. Kaplan-Meier plotter analysis revealed that ATF3 expression was positively related to the overall survival of GC patients. In particular, lower levels of ATF3 were observed in cisplatin-resistant SGC7901/DDP and BGC823/DDP relative to their parental cells. Notably, ATF3 elevation sensitized cisplatin-resistant cells to cisplatin. Mechanically, compared with parental cells, SGC7901/DDP and BGC823/DDP cells exhibited lower ferroptosis evident by lower ROS, MDA and lipid peroxidation and higher intracellular GSH levels. However, ATF3 elevated ferroptosis in SGC7901/DDP and BGC823/DDP cells. Intriguingly, ATF3 overexpression together with ferroptosis activator erastin or RSL3 treatment further enhanced ferroptosis and cisplatin resistance; however, the ferroptosis suppressor liproxstatin-1 reversed the function of ATF3 in ferroptosis and cisplatin resistance. Additionally, cisplatin-resistant cells exhibited stronger activation of Nrf2/Keap1/xCT signaling relative to parental cells, which was restrained by ATF3 up-regulation. Importantly, restoring Nrf2 signaling overturned ATF3-mediated ferroptosis and cisplatin resistance.
conclusionATF3 may sensitize GC cells to cisplatin by induction of ferroptosis via blocking Nrf2/Keap1/xCT signaling, supporting a promising therapeutic approach for overcoming chemoresistance in GC.
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