Baculoviral Inhibitor of Apoptosis Repeat Containing 5 (BIRC5) Regulates Cancer Stem Cell Properties and Epithelial-Mesenchymal Transition in Human Breast Cancer Cells.

Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) (survivin) is known to play an important role in cell survival and tumor progression; however, its involvement in cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) in breast cancer remain unclear. In this study, we investigated the role of BIRC5 in regulating CSC-like characteristics and EMT in human breast cancer cells. Analysis of public datasets revealed that BIRC5 expression is significantly elevated in breast cancer tissues and is associated with poor patient prognosis. Treatment with CSC-inducing conditioned medium (CSC-CM) increased the expression of CSC markers, including CD44, ALDH1A1, and ALDH1A3. Silencing of BIRC5 using siRNA reduced the expression of CSC-associated markers as well as pluripotency-related transcription factors (Sox2, Oct4, and Nanog). In addition, BIRC5 knockdown significantly decreased sphere-forming ability, indicating reduced self-renewal capacity. Furthermore, suppression of BIRC5 altered EMT-related protein expression, as evidenced by increased E-cadherin and decreased N-cadherin, Vimentin, and EMT-associated transcription factors (Snail, Slug, Twist, and Zeb1). In addition, BIRC5 knockdown also significantly reduced cell migration and invasion. These results suggest that BIRC5 is involved in the regulation of CSC properties and EMT in breast cancer cells and may contribute to tumor progression.