ArticleCell death & disease2014
Inhibition of eIF2α dephosphorylation enhances TRAIL-induced apoptosis in hepatoma cells.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
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- The Preventive Effects of Salubrinal against Pyrethroid-Induced Disruption of Adult Hippocampal Neurogenesis in Mice.International journal of molecular sciences · 2023Article
- An initial characterisation of the Unfolded Protein Response pathway in haematopoietic canine cancer cell lines - a necessary step for the future development of new therapies in dogs with neoplasia.Journal of veterinary research · 2023Article
- Heme-regulated inhibitor: an overlooked eIF2α kinase in cancer investigations.Medical oncology (Northwood, London, England) · 2022Review
- Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PMAntioxidants (Basel, Switzerland) · 2021Article
- Salubrinal Exposes Anticancer Properties in Inflammatory Breast Cancer Cells by Manipulating the Endoplasmic Reticulum Stress Pathway.Frontiers in oncology · 2021Article
- Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model.Molecular neurobiology · 2020Article
- Stress Management: Death Receptor Signalling and Cross-Talks with the Unfolded Protein Response in Cancer.Cancers · 2020Review
- Stress granule: A promising target for cancer treatment.British journal of pharmacology · 2019Review
- Proteostasis In The Endoplasmic Reticulum: Road to Cure.Cancers · 2019Review
- Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner.Cell death & disease · 2019Article
- Unfolded Protein Response (UPR) in Survival, Dormancy, Immunosuppression, Metastasis, and Treatments of Cancer Cells.International journal of molecular sciences · 2019Review
- An integrated stress response via PKR suppresses HER2+ cancers and improves trastuzumab therapy.Nature communications · 2019Article
- The regulatory protein GADD34 inhibits TRAIL-induced apoptosis via TRAF6/ERK-dependent stabilization of myeloid cell leukemia 1 in liver cancer cells.The Journal of biological chemistry · 2019Article
- Targeting KPNB1 overcomes TRAIL resistance by regulating DR5, Mcl-1 and FLIP in glioblastoma cells.Cell death & disease · 2019Article
- Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis.Brain : a journal of neurology · 2019Article
- EGFR confers radioresistance in human oropharyngeal carcinoma by activating endoplasmic reticulum stress signaling PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78.Cancer medicine · 2018Article
- Sevoflurane relieves hepatic ischemia-reperfusion injury by inhibiting the expression of Grp78.Bioscience reports · 2018Article
- The double-edged sword of endoplasmic reticulum stress in uremic sarcopenia through myogenesis perturbation.Journal of cachexia, sarcopenia and muscle · 2018Article
- Trichosanthin enhances sensitivity of non-small cell lung cancer (NSCLC) TRAIL-resistance cells.International journal of biological sciences · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an inducer of cancer cell death that holds promise in cancer therapy. Cancer cells are more susceptible than normal cells to the cell-death-inducing effects of TRAIL. However, a variety of cancer cells are resistant to TRAIL through complex mechanisms. Here, we investigate the effects of inhibition of eukaryotic initiation factor 2 subunit α (eIF2α) dephosphorylation on TRAIL-induced apoptosis in hepatoma cells. Treatment of hepatoma cells with salubrinal, an inhibitor of eIF2α dephosphorylation, enhances TRAIL-induced eIF2α phosphorylation, CCAAT/enhancer-binding protein homologous protein (CHOP) expression and caspase activation. Salubrinal enhances TRAIL-induced apoptosis, which could be abrogated by caspase inhibitor. Overexpression of phosphomimetic eIF2α (S51D) enhances TRAIL-induced CHOP expression, caspase 7 and PARP cleavage and apoptosis. By contrast, overexpression of phosphodeficient eIF2α (S51A) abrogates the stimulation of TRAIL-induced apoptosis by salubrinal. Moreover, knockdown of growth arrest and DNA damage-inducible protein 34 (GADD34), which recruits protein phosphatase 1 to dephosphorylate eIF2α, enhances TRAIL-induced eIF2α phosphorylation, CHOP expression, caspase activation and apoptosis. Furthermore, the sensitization of hepatoma cells to TRAIL by salubrinal is dependent on CHOP. Knockdown of CHOP abrogates the stimulation of TRAIL-induced caspase activation and apoptosis by salubrinal. Combination of salubrinal and TRAIL leads to increased expression of Bim, a CHOP-regulated proapoptotic protein. Bim knockdown blunts the stimulatory effect of salubrinal on TRAIL-induced apoptosis. Collectively, these findings suggest that inhibition of eIF2α dephosphorylation may lead to synthetic lethality in TRAIL-treated hepatoma cells.
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