STAT5 in Cancer and Immunity
Journal of Interferon and Cytokine Research
Signal transducers and activators of transcription 5 (STAT5a and STAT5b) are highly homologous proteins that are encoded by two separate genes and are activated by Janusactivated kinases (JAK) downstream of cytokine receptors. STAT5 proteins are activated by a wide variety of hematopoietic and non-hematopoietic cytokines and growth factors, all of which use the JAK-STAT signalling pathway as their main mode of signal transduction. STAT5 proteins critically regulate vital cellular functions such
... as proliferation, differentiation and survival. The physiological importance of STAT5 proteins is underscored by the plethora of primary human tumours that have aberrant constitutive activation of these proteins, which significantly contributes to tumour cell survival and malignant progression of disease. STAT5 plays an important role in the maintenance of normal immune function and homeostasis, both of which are regulated by specific members of IL-2 family of cytokines, which share a common gamma chain (γ c ) in their receptor complex. STAT5 critically mediates the biological actions of members of the γ c family of cytokines in the immune system. Essentially, STAT5 plays a critical role in the function and development of Tregs and consistently activated STAT5 is associated with a suppression in antitumour immunity and an increase in proliferation, invasion and survival of tumour cells. Thus, therapeutic targeting of STAT5 is promising in cancer.