Downregulation of inhibitor of apoptosis protein induces apoptosis and suppresses stemness maintenance in testicular teratoma

Abstract

Inhibitors of apoptosis (IAPs) are a family of cell death inhibitors found in viruses and metazoans that physically interact with a variety of pro-apoptotic proteins and inhibit apoptosis induced by diverse stimuli. Melanoma IAP (ML-IAP) is a potent anti-apoptotic protein that is strongly upregulated in melanoma and confers protection against a variety of pro-apoptotic stimuli. In the present study, it was revealed that ML-IAP was expressed at high levels in testicular teratoma. Deletion and mutational analysis demonstrated that ML-IAP silencing significantly decreased P19 cell proliferation while inducing cell cycle arrest and apoptosis. ML-IAP knockdown significantly induced caspase-3/8/9-mediated apoptosis in P19 cells. In addition, metabolism and stemness maintenance in P19 cells were suppressed by ML-IAP knockdown. These results indicated that ML-IAP silencing is a powerful inducer of apoptosis mediated by cell death receptors and may function as a direct activator of downstream effector caspases.