STATs in oncogenesis

Since their discovery as key mediators of cytokine signaling, considerable progress has been made in defining the structure-function relationships of Signal Transducers and Activators of Transcription (STATs), In addition to their central roles in normal cell signaling, recent studies have demonstra ted that diverse oncoproteins can activate specific STATs (particularly Sta ll and Stat5) and that constitutively-activated STAT signaling directly con tributes to oncogenesis, Furthermore, extensive surveys of primary tumors a nd cell lines derived from tumors indicate that inappropriate activation of specific STATs occurs with surprisingly high frequency in a wide variety o f human cancers. Together, these findings provide compelling evidence that aberrant STAT activation associated with oncogenesis is not merely adventit ious but instead contributes to the process of malignant transformation. Th ese studies are beginning to reveal the molecular mechanisms leading to STA T activation in the context of oncogenesis, and candidate genes regulated b y STATs that may contribute to oncogenesis are being identified. Recent stu dies suggest that activated STAT signaling participates in oncogenesis by s timulating cell proliferation and preventing apoptosis, This review present s the evidence for critical roles of STATs in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic u nderstanding of STAT signaling.