Signal transducers and activators of transcription 5 (STAT5a and STAT5b) are highly homologous
proteins that are encoded by 2 separate genes and are activated by Janus-activated
kinases (JAK) downstream of
cytokine receptors. STAT5
proteins are activated by a wide variety of hematopoietic and nonhematopoietic
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
tumors that have aberrant constitutive activation of these
proteins, which significantly contributes to
tumor 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 antitumor immunity and an increase in proliferation, invasion, and survival of
tumor cells. Thus, therapeutic targeting of STAT5 is promising in
cancer.