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Myeloma

Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in multiple myeloma

Leukemia volume 27, pages 1165–1171 (2013)Cite this article

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Abstract

Multiple myeloma (MM) is an incurable malignancy of terminally differentiated B-lymphoid cells. Here, we investigate the role of Fas apoptosis inhibitory molecule (FAIM) in MM. We demonstrate that insulin-like growth factor 1 (IGF-1) treatment upregulated 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 upregulation of IRF4 expression by IGF-1 treatment of MM cells is abrogated when FAIM expression is silenced or Akt activation is inhibited. Thus, FAIM modulates IGF-1-induced Akt activation and IRF4 expression and has 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 is shown to correlate with poorer survival outcomes of newly diagnosed MM patients treated with stem cell transplantation or 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.

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Acknowledgements

We thank Ong MH for technical assistance and members of the laboratory for insightful discussions and the Biomedical Research Council of the Agency for Science, Technology and Research for funding this research.

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Authors and Affiliations

  1. Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Republic of Singapore

    J Huo, S Xu & K-P Lam

  2. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore

    S Xu & K-P Lam

  3. Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Republic of Singapore

    B Lin & W-J Chng

  4. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore

    W-J Chng

  5. Experimental Therapeutics Programme, The Cancer Science Institute, National University of Singapore, Republic of Singapore

    W-J Chng

  6. Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore

    K-P Lam

  7. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore

    K-P Lam

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Correspondence to K-P Lam.

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Huo, J., Xu, S., Lin, B. et al. Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in multiple myeloma. Leukemia 27, 1165–1171 (2013). https://doi.org/10.1038/leu.2012.326

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