RelB acts as a molecular switch driving chronic inflammation in glioblastoma multiforme
| Autor: | Debolina D. Biswas, Tomasz Kordula, Angela S. Gupta, Karli Mockenhaupt, Lashardai N. Brown, Michael R. Waters |
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| Rok vydání: | 2018 |
| Předmět: |
Cancer Research
Inflammation lcsh:RC254-282 Article Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine medicine Molecular Biology Transcription factor 030304 developmental biology 0303 health sciences biology Microglia YY1 Sirtuin 1 RELB Oncostatin M lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health nervous system diseases CNS cancer medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Cancer research medicine.symptom |
| Zdroj: | Oncogenesis Oncogenesis, Vol 8, Iss 6, Pp 1-14 (2019) |
| ISSN: | 2157-9024 |
| Popis: | Glioblastoma multiforme (GBM) is a primary brain tumor characterized by extensive necrosis and immunosuppressive inflammation. The mechanisms by which this inflammation develops and persists in GBM remain elusive. We identified two cytokines interleukin-1β (IL-1) and oncostatin M (OSM) that strongly negatively correlate with patient survival. We found that these cytokines activate RelB/p50 complexes by a canonical NF-κB pathway, which surprisingly drives expression of proinflammatory cytokines in GBM cells, but leads to their inhibition in non-transformed astrocytes. We discovered that one allele of the gene encoding deacetylase Sirtuin 1 (SIRT1), needed for repression of cytokine genes, is deleted in 80% of GBM tumors. Furthermore, RelB specifically interacts with a transcription factor Yin Yang 1 (YY1) in GBM cells and activates GBM-specific gene expression programs. As a result, GBM cells continuously secrete proinflammatory cytokines and factors attracting/activating glioma-associated microglia/macrophages and thus, promote a feedforward inflammatory loop. |
| Databáze: | OpenAIRE |
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