Significant impact of survivin on myeloma cell growth

Abstract

Survivin is a fascinating member of the inhibitor of apoptosis protein (IAP) family with its dual roles in mitosis and apoptosis, and emerges as an attractive target for cancer therapy. Multiple myeloma (MM) is a plasma cell malignancy, characterized by deregulated proliferation, cell-death processes and fatal outcome. We thus investigated survivin expression in myeloma cells and its role in MM biology to evaluate its potential interest as a target in MM treatment. Our results describe the cancerspecific overexpression of survivin in myeloma cells and show a significant correlation between survivin expression at protein level and clinical course of MM. Moreover, survivin knockdown by RNA interference led to growth rate inhibition of myeloma cells related to apoptosis induction and deep cell-cycle disruption. Finally, survivin knockdown sensitized myeloma cells to conventional anti-myeloma agents. Altogether, these data argue for the interest to evaluate survivin antagonists in MM treatment.

Concomitant downregulation of proliferation/survival pathways dependent on FGF-R3, JAK2 and BCMA in human multiple myeloma cells by multi-kinase targeting

“…The decrease in survivin expression, which was not appreciated at RNA level, was likely a consequence of PI3K/AKT pathway inhibition, as previously shown by specific AKT inhibition in the MM cell context [32]. Notably, modulation of Mcl-1 and survivin, as well as AKT, may have therapeutic relevance in this disease [25,47,49]. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 M a n u s c r i p …”

“…3B), known as survival factors in myeloma cells [9,25]. Expression levels of Bcl-2 were not affected by drug treatment (not shown).…”

Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan

“…We found that echinomycin or siRNA against HIF-1α specifically blocked both basal and IGF-1-induced survivin levels. Survivin is widely expressed in many types of established myeloma cell lines and contributes to cell survival (28,44). Romagnoli et al (44) showed that siRNA-mediated inhibition of survivin expression sensitizes myeloma cells to conventional antimyeloma agents, including melphalan.…”

“…Survivin is widely expressed in many types of established myeloma cell lines and contributes to cell survival (28,44). Romagnoli et al (44) showed that siRNA-mediated inhibition of survivin expression sensitizes myeloma cells to conventional antimyeloma agents, including melphalan. Furthermore, Peng et al found that HIF-1 regulates survivin expression in breast cancer cells (34).…”

Immune Modulation by Zoledronic Acid in Human Myeloma: An Advantageous Cross-Talk between Vγ9Vδ2 T Cells, αβ CD8+ T Cells, Regulatory T Cells, and Dendritic Cells

“…mDC ZA+ were very effective in both CTRL and MM NR, and resulted in the proliferative expansion of but also in those NR MM in which gd T cell proliferation was reinstated. SRV was selected as a prototypic tumor-associated Ag because it is expressed by myeloma cells and contributes to their survival (38). SRV-specific T cells have been tolerized but not deleted from the MM T cell repertoire (23), and their effector functions can be reinstated by appropriate SRV presentation and T cell stimulation (39,40).…”