Our results revealed that the simultaneous existence of YB-1 and the other four (SOX2, POU3F2, OCT-4, and OLIG1) or five (SOX2, SALL2, OCT-4, POU3F2, and Bmi-1) transcription factors reverted YB-1-deleted melanoma stem cells or breast cancer stem cells, respectively, into cancer stem cells. The gene discussed is SOX2; the disease is cancer.