Significant impact of survivin on myeloma cell growth.
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 cancer-specific 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.
Romagnoli
M
M
1INSERM, UMR 601, 9 quai Moncousu, Nantes, F-44093, France.
Trichet
V
V
David
C
C
Clément
M
M
Moreau
P
P
Bataille
R
R
Barillé-Nion
S
S
D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D034622:RNA Interference; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin