ArticleInternational journal of molecular sciences2018
Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 57 citations in OpenAlex.
- ACSL3 inhibits ferroptosis in gastric cancer through the activation of unfolded protein response following endoplasmic reticulum stress.Cell death & disease · 2026Article
- Phosphoenolpyruvate carboxykinase 2 as a prognostic biomarker: expression and clinical significance in Group 3 and Group 4 medulloblastoma.Journal of neuro-oncology · 2026Article
- Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma.Cell death discovery · 2026Article
- The Dual Role of SLC7A11 in Colorectal Cancer Ferroptosis: From Molecular Mechanisms to Therapeutic Opportunities.OncoTargets and therapy · 2026Review
- Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-Modification Promotes Lenvatinib Resistance in HCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Disulfidptosis, A Novel Cell Death Pathway: Molecular Landscape and Therapeutic Implications.Aging and disease · 2024Review
- Baicalein improves the chemoresistance of ovarian cancer through regulation of CirSLC7A6.Journal of ovarian research · 2023Article
- Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice.Aging cell · 2023Article
- Mechanism of cisplatin resistance in gastric cancer and associated microRNAs.Cancer chemotherapy and pharmacology · 2023Review
- Growth differentiation factor 15 induces cisplatin resistance through upregulation of xCT expression and glutathione synthesis in gastric cancer.Cancer science · 2023Article
- Attenuation of Piwil2 induced by hypoxic postconditioning prevents cerebral ischemic injury by inhibiting CREB2 promoter methylation.Brain pathology (Zurich, Switzerland) · 2023Article
- The integrated stress response in cancer progression: a force for plasticity and resistance.Frontiers in oncology · 2023Review
- Cysteine dioxygenase 1 attenuates the proliferation via inducing oxidative stress and integrated stress response in gastric cancer cells.Cell death discovery · 2022Article
- Exposure to Heated Tobacco Products Aerosol Causes Acute Stress Responses in the Lung of Mouse.Antioxidants (Basel, Switzerland) · 2022Article
- GCN2: roles in tumour development and progression.Biochemical Society transactions · 2022Review
- Insight into the mitochondrial unfolded protein response and cancer: opportunities and challenges.Cell & bioscience · 2022Review
- Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxicity via SLC7A11-Mediated Redox Collapse.Cancers · 2022Article
- Amino Acid Metabolism in Cancer Drug Resistance.Cells · 2022Review
- The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer.Frontiers in oncology · 2022Review
- Involvement of microRNA/cystine/glutamate transporter in cold-stressed gastric mucosa injury.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The integrated stress response (ISR) pathway is essential for adaption of various stresses and is related to mitochondrion-to-nucleus communication. Mitochondrial dysfunction-induced reactive oxygen species (ROS) was demonstrated to activate general control nonderepressible 2 (GCN2)⁻eukaryotic translation initiation factor 2α (eIF2α)⁻activating transcription factor-4 (ATF4) pathway-mediated cisplatin resistance of human gastric cancer cells. However, whether or how ISR activation per se could enhance chemoresistance remains unclear. In this study, we used eIF2α phosphatase inhibitor salubrinal to activate the ISR pathway and found that salubrinal reduced susceptibility to cisplatin. Moreover, salubrinal up-regulated ATF4-modulated gene expression, and knockdown of ATF4 attenuated salubrinal-induced drug resistance, suggesting that ATF4-modulated genes contribute to the process. The ATF4-modulated genes, xCT (a cystine/glutamate anti-transporter), tribbles-related protein 3 (TRB3), heme oxygenase 1 (HO-1), and phosphoenolpyruvate carboxykinase 2 (PCK2), were associated with a poorer prognosis for gastric cancer patients. By silencing individual genes, we found that xCT, but not TRB3, HO-1, or PCK2, is responsible for salubrinal-induced cisplatin resistance. In addition, salubrinal increased intracellular glutathione (GSH) and decreased cisplatin-induced lipid peroxidation. Salubrinal-induced cisplatin resistance was attenuated by inhibition of xCT and GSH biosynthesis. In conclusion, our results suggest that ISR activation by salubrinal up-regulates ATF4-modulated gene expression, increases GSH synthesis, and decreases cisplatin-induced oxidative damage, which contribute to cisplatin resistance in gastric cancer cells.
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.