BIRC5 regulates the IGFBP-3-induced autocrine loop in cancer stem cells.

Abstract

Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is also known as survivin. BIRC5 is overexpressed in various carcinomas and is involved in cell growth and apoptosis. BIRC5, a member of the apoptosis inhibitor (IAP) family, negatively regulates apoptosis or programmed cell death by inhibiting caspase activation. Due to these properties, overexpression of BIRC5 enables specific survival and division associated with cancer malignancies. In addition, BIRC5 is highly expressed in stem cells, but not present at all in terminally differentiated cells. On this basis, there is speculation that BIRC5 may be involved in the regulation of cancer stem cells (CSCs), but few study results have been reported. In addition, the molecular mechanisms of BIRC5 regulation are not yet well understood. Through the present study, it was confirmed that BIRC5 is a key factor regulating CSCs and epithelial to mesenchymal transition (EMT) phenomena. BIRC5 was simultaneously overexpressed in lung cancer stem cells (LCSCs) and glioma stem cells (GSCs), and when the expression was suppressed, the characteristics of CSCs disappeared. In addition, IGFBP-3, a secreted factor regulated by BIRC5, is involved in signaling mechanisms that regulate cancer stem cells and EMT, and IGFBP-3 forms an autocrine chain. Based on these results, BIRC5 is proposed as a novel therapeutic target protein for LCSCs and GSCs.