ArticleOncoimmunology
PKR and GCN2 stress kinases promote an ER stress-independent eIF2α phosphorylation responsible for calreticulin exposure in melanoma cells.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 63 citations in OpenAlex.
- Immunogenic Cell Death Induced by EEO in Breast Cancer Cells Promotes Dendritic Cell Activation in a CRT-Dependent Manner.Life (Basel, Switzerland) · 2026Article
- Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma.Cell death discovery · 2026Article
- Induction of immunogenic cell death by active components of natural products reshaping the tumor microenvironment for enhanced antitumor immunity.Frontiers in pharmacology · 2026Review
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- Isolation of New Chemical Modulators of the Interaction Between HIV-1 Integrase and the Cellular Restriction Factor GCN2.Viruses · 2025Article
- Metal-based immunogenic cell death inducers for cancer immunotherapy.Chemical science · 2025Review
- Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC.Cancer biomarkers : section A of Disease markers · 2025Article
- Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Translational oncology · 2024Review
- Targeting immunogenic cell stress and death for cancer therapy.Nature reviews. Drug discovery · 2024Review
- FSP1 is a predictive biomarker of osteosarcoma cells' susceptibility to ferroptotic cell death and a potential therapeutic target.Cell death discovery · 2024Article
- Natural compound Alternol actives multiple endoplasmic reticulum stress-responding pathways contributing to cell death.Frontiers in pharmacology · 2024Article
- AMPK activation induces immunogenic cell death in AML.Blood advances · 2023Article
- Quantification of the Chemical Chaperone 4-Phenylbutyric Acid (4-PBA) in Cell Culture Media via LC-HRMS: Applications in Fields of Neurodegeneration and Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Chemotherapeutic and targeted drugs-induced immunogenic cell death in cancer models and antitumor therapy: An update review.Frontiers in pharmacology · 2023Review
- [Comparison of three commercial photosensitizers for efficiency of inducing immunogenic cell death in anti-tumor immunotherapy].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Article
- Protein synthesis inhibition and loss of homeostatic functions in astrocytes from an Alzheimer's disease mouse model: a role for ER-mitochondria interaction.Cell death & disease · 2022Article
- Review
- A novel inflammatory response-related signature predicts the prognosis of cutaneous melanoma and the effect of antitumor drugs.World journal of surgical oncology · 2022Article
- Role of HMGB1 in Cutaneous Melanoma: State of the Art.International journal of molecular sciences · 2022Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunogenic cell death (ICD) process represents a novel therapeutic approach to treat tumours, in which cytotoxic compounds promote both cancer cell death and the emission of damage-associated molecular patterns (DAMPs) from dying cells, to activate the immune system against the malignancy. Therefore, we explored the possibility to stimulate the key molecular players with a pivotal role in the execution of the ICD program in melanoma cells. To this aim, we used the pro-ICD agents mitoxantrone and doxorubicin and found that both agents could induce cell death and stimulate the release/exposure of the strictly required DAMPs in melanoma cells: i) calreticulin (CRT) exposure on the cell membrane; ii) ATP secretion; iii) type I IFNs gene up-regulation and iv) HMGB1 secretion, highlighting no interference by oncogenic BRAF. Importantly, although the ER stress-related PERK activation has been linked to CRT externalization, through the phosphorylation of eIF2α, we found that this stress pathway together with PERK were not involved in melanoma cells. Notably, we identified PKR and GCN2 as key mediators of eIF2α phosphorylation, facilitating the translocation of CTR on melanoma cells surface, under pro-ICD drugs stimulation. Therefore, our data indicate that pro-ICD drugs are able to stimulate the production/release of DAMPs in melanoma cells at least in vitro, indicating in this approach a potential new valuable therapeutic strategy to treat human skin melanoma malignancy.
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