The NF-κB RelB protein is an oncogenic driver of mesenchymal glioma
| Autor: | Ian F. Parney, Dong W. Lee, Raquel Sitcheran, Dhivya Ramakrishnan, John P Valenta, Kayla J. Bayless |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Mouse
Carcinogenesis lcsh:Medicine medicine.disease_cause Mesoderm Mice 0302 clinical medicine Lectins Molecular Cell Biology Basic Helix-Loop-Helix Transcription Factors lcsh:Science Neurological Tumors 0303 health sciences Multidisciplinary Brain Neoplasms RELB NF-kappa B Glioma Animal Models Signaling in Selected Disciplines 3. Good health Oncology 030220 oncology & carcinogenesis Neoplastic Stem Cells Medicine Research Article Signal Transduction Cell Survival Transcription Factor RelB Mice Nude Nerve Tissue Proteins Biology Molecular Genetics OLIG2 03 medical and health sciences Model Organisms Adipokines Cancer stem cell Cell Line Tumor Genetics Cancer Genetics medicine Animals Humans Neoplasm Invasiveness Gene Regulation Chitinase-3-Like Protein 1 Cell Proliferation 030304 developmental biology Oncogenic Signaling Mesenchymal stem cell lcsh:R Cancers and Neoplasms Oligodendrocyte Transcription Factor 2 medicine.disease nervous system diseases Tumor progression Cancer research lcsh:Q Gene Function |
| Zdroj: | PLoS ONE, Vol 8, Iss 2, p e57489 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | High-grade gliomas, such as glioblastomas (GBMs), are very aggressive, invasive brain tumors with low patient survival rates. The recent identification of distinct glioma tumor subtypes offers the potential for understanding disease pathogenesis, responses to treatment and identification of molecular targets for personalized cancer therapies. However, the key alterations that drive tumorigenesis within each subtype are still poorly understood. Although aberrant NF-κB activity has been implicated in glioma, the roles of specific members of this protein family in tumorigenesis and pathogenesis have not been elucidated. In this study, we show that the NF-κB protein RelB is expressed in a particularly aggressive mesenchymal subtype of glioma, and loss of RelB significantly attenuated glioma cell survival, motility and invasion. We find that RelB promotes the expression of mesenchymal genes including YKL-40, a marker of the MES glioma subtype. Additionally, RelB regulates expression of Olig2, a regulator of cancer stem cell proliferation and a candidate marker for the cell of origin in glioma. Furthermore, loss of RelB in glioma cells significantly diminished tumor growth in orthotopic mouse xenografts. The relevance of our studies for human disease was confirmed by analysis of a human GBM genome database, which revealed that high RelB expression strongly correlates with rapid tumor progression and poor patient survival rates. Thus, our findings demonstrate that RelB is an oncogenic driver of mesenchymal glioma tumor growth and invasion, highlighting the therapeutic potential of inhibiting the noncanonical NF-κB (RelB-mediated) pathway to treat these deadly tumors. |
| Databáze: | OpenAIRE |
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