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Fas Apoptosis Inhibitory Molecule (FAIM) is up-regulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in Multiple Myeloma.
MedLine Citation:
PMID:  23138182     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multiple myeloma (MM) is an incurable malignancy of terminally differentiated B lymphoid cells. Here, we investigated the role of Fas apoptosis inhibitory molecule (FAIM) in MM. We demonstrated that IGF-1 treatment up-regulated FAIM expression in MM cells in a dose-dependent manner. Silencing of FAIM expression attenuates Akt signaling downstream of IGF-1 and compromises the viability of MM cells. We further showed that IGF-1 stimulation of MM cells leads to enhanced expression of IRF4, a known 'addictive' factor for MM. This up-regulation of IRF4 expression by IGF-1 treatment of MM cells is abrogated when FAIM expression is silenced or Akt activation is inhibited. Thus, FAIM regulates IGF-1-induced Akt activation and IRF4 expression and plays a role in MM cell survival. Consistent with these findings, FAIM expression is shown to be higher in plasma cells of symptomatic MM patients compared with normal individuals or patients with premalignant conditions. Moreover, a higher level of FAIM expression was shown to correlate with poorer survival outcomes of newly diagnosed MM patients treated with stem cell transplantation or the relapsed MM patients treated in clinical trials with Bortezomib. Thus taken together, our study reveals a novel as well as clinically relevant role for FAIM in MM.Leukemia accepted article preview online, 9 November 2012; doi:10.1038/leu.2012.326.
Authors:
J Huo; S Xu; B Lin; W-J Chng; K-P Lam
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-09
Journal Detail:
Title:  Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K     Volume:  -     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), Republic of Singapore, Singapore, Singapore.
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