Title |
Frequent Engagement of RelB Activation Is Critical for Cell Survival in Multiple Myeloma
|
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Published in |
PLOS ONE, March 2013
|
DOI | 10.1371/journal.pone.0059127 |
Pubmed ID | |
Authors |
Françoise Cormier, Hélène Monjanel, Claire Fabre, Katy Billot, Elène Sapharikas, Fanny Chereau, Didier Bordereaux, Thierry J. Molina, Hervé Avet-Loiseau, Véronique Baud |
Abstract |
The NF-κB family of transcription factors has emerged as a key player in the pathogenesis of multiple myeloma (MM). NF-κB is activated by at least two major signaling pathways. The classical pathway results in the activation of mainly RelA containing dimers, whereas the alternative pathway leads to the activation of RelB/p52 and RelB/p50 heterodimers. Activating mutations in regulators of the alternative pathway have been identified in 17% of MM patients. However, the status of RelB activation per se and its role in the regulation of cell survival in MM has not been investigated. Here, we reveal that 40% of newly diagnosed MM patients have a constitutive RelB DNA-binding activity in CD138(+) tumor cells, and we show an association with increased expression of a subset of anti-apoptotic NF-κB target genes, such as cIAP2. Furthermore, we demonstrate that RelB exerts a crucial anti-apoptotic activity in MM cells. Our findings indicate that RelB activation is key for promoting MM cell survival through the upregulation of anti-apoptotic proteins. Altogether, our study provides the framework for the development of new molecules targeting RelB in the treatment of MM. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 50% |
Mexico | 1 | 25% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
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Unknown | 42 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 7 | 17% |
Student > Ph. D. Student | 7 | 17% |
Student > Bachelor | 6 | 14% |
Student > Master | 6 | 14% |
Other | 5 | 12% |
Other | 5 | 12% |
Unknown | 6 | 14% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 11 | 26% |
Medicine and Dentistry | 9 | 21% |
Agricultural and Biological Sciences | 8 | 19% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Immunology and Microbiology | 2 | 5% |
Other | 3 | 7% |
Unknown | 7 | 17% |