Open AccessFrequent Engagement of RelB Activation Is Critical for Cell Survival in Multiple Myeloma
Author(s) -
Franc̊oise Cormier,
Hélène Monjanel,
Claire Fabre,
Katy Billot,
Elène Sapharikas,
Fanny Chéreau,
Didier Bordereaux,
Thierry Jo Molina,
Hervé Avet-Loiseau,
Véronique Baud
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0059127
Subject(s) - relb , p50 , downregulation and upregulation , cancer research , apoptosis , microbiology and biotechnology , transcription factor , nf κb , multiple myeloma , signal transduction , nfkb1 , biology , chemistry , immunology , gene , genetics
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.