ArticleCell death discovery2018
IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK dipendent autophagy.
Article in Cell death discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- The Link Between Endoplasmic Reticulum Stress and Lysosomal Dysfunction Under Oxidative Stress in Cancer Cells.Biomolecules · 2025Review
- Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.Theranostics · 2024Article
- Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma?Cancers · 2022Review
- Monitoring Mitochondrial Function inInsects · 2021Article
- Review
- Atiprimod triggered apoptotic cell death via acting on PERK/eIF2α/ATF4/CHOP and STAT3/NF-ΚB axis in MDA-MB-231 and MDA-MB-468 breast cancer cells.Molecular biology reports · 2021Article
- The molecular mechanism of a novel derivative of BTO-956 induced apoptosis in human myelomonocytic lymphoma cells.Apoptosis : an international journal on programmed cell death · 2021Article
- Huotan Jiedu Tongluo Decoction Inhibits Balloon-Injury-Induced Carotid Artery Intimal Hyperplasia in the Rat through the PERK-eIF2Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Mechanism of inositol-requiring enzyme 1-alpha inhibition in endoplasmic reticulum stress and apoptosis in ovarian cancer cells.Journal of cell communication and signaling · 2020Article
- Article
- Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis.International journal of molecular sciences · 2019Review
- Cathepsin B: A sellsword of cancer progression.Cancer letters · 2019Review
- Autophagy Plays a Critical Role in Insulin Resistance- Mediated Chemoresistance in Hepatocellular Carcinoma Cells by Regulating the ER Stress.Journal of Cancer · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase. GSK2606414, a PERK inhibitor, and PERK specific siRNA prevent eIF2α down-regulation and restore cell survival. Degradation of this protein is due to autophagy, as it is prevented by bafilomycin and not by proteasome inhibition. Furthermore, activation of the autophagy flux is PERK dependent. Also the Cathepsin B inhibitor CA074 prevents eIF2α from degradation and reduces cell death. Altogether, these results show that IRE1α deficiency in ER stressed cells leads to an unexpected decrease of eIF2α, an important molecule for protein translation, through PERK dependent autophagy. Thus, IRE1/XBP1 inhibitors may represent a feasible strategy for tumor therapy, while PERK inhibitors may vanish the goal.
Identifiers
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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.