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Autophagy regulates selective HMGB1 release in tumor cells that are destined to die
Open accessAbstract
Macroautophagy (hereafter referred to as autophagy) can increase or decrease the amount of cell death in response to various stimuli. To test whether autophagy also controls the characteristics associated with dying cells, we studied tumor cell killing by epidermal growth factor receptor-targeted diphtheria toxin (DT-EGF). DT-EGF kills epithelial and glioblastoma tumor cells with similar efficiency but by different mechanisms that depend on whether the cells activate autophagy when treated with the drug. Dying cells in which autophagy is induced selectively release the immune modulator high-mobility group B1 (HMGB1) without causing lysis of the cell membrane and classical necrosis. Conversely, cells that are killed by DT-EGF where autophagy is blocked, activate caspases but retain HMGB1. These data suggest that it may be feasible to manipulate the immunogenicity of dying cells by increasing or decreasing autophagy.
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“In one model of immunogenic cell death, influenza virus-infected Bax−/−Bak−/− mouse embryonic fibroblasts (which cannot engage apoptosis via the mitochondrial pathway) were induced to undergo non-apoptotic cell death accompanied by massive autophagy 65 and immunization with these DNA-damaged Bax−/−Bak−/− cells was found to be more efficient in facilitating the cross-priming of antigen-specific CD8”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [65]
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Metadata
- Authors
- Thorburn, J., Horita, H., Redzic, J., Hansen, K., Frankel, A. E., & Thorburn, A.
- Affiliations
- University of Colorado Anschutz (US)
- Baylor Scott & White Health (US)
- Corresponding author
- Thorburn, A
- Venue
- Cell Death & Differentiation
- Published
- 2008-10-10
- Volume
- 16
- Issue
- 1
- Pages
- 175-183
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC2605182
- OpenAlex
- W2080208339
- Cited by
- 268
- References
- 43
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 17 · 2022: 16 · 2021: 19 · 2020: 16 · 2019: 13 · 2018: 14 · 2017: 19 · 2016: 22 · 2015: 17 · 2014: 19 · 2013: 18 · 2012: 11
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of California, San Francisco
- National Cancer Institute (CA111421, R01CA111421, P30CA046934)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- autophagy, HMGB1, cancer cell death, diphtheria toxin, epidermal growth factor receptor, glioblastoma, epithelial cancer cells, caspase activation, immunogenic cell death, tumor immunology
- MeSH terms
- Autophagy, Diphtheria Toxin, Epidermal Growth Factor, Glioblastoma, Humans, Immunologic Factors, Neoplasm Proteins, Neoplasms, Glandular and Epithelial, Recombinant Fusion Proteins, HMGB1 Protein, Cell Line, Tumor
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