STAT Proteins in Cancerogenesis and Therapy of Malignancies

Signal transducers and activators of transcription (STAT) proteins are a 7-member family of cytoplasmic transcription factors that participate in signal transduction by cytokines, hormones, and growth factors. STAT proteins control the most important cellular processes, including survival, proliferation and differentiation. A great number of cytokines and other factors in different cell types activate STAT1, STAT3 and STAT5 and in this manner regulate processes such as cellular proliferation, differentiation and survival. STATs such as STAT4 and STAT6 have a more specific effect and are engaged in the differentiation of T helper cell populations. Given the critical roles of STAT proteins it has been established in many studies that STAT3 and STAT5 are oncogenes that can contribute to cellular transformation by increasing proliferation and slowing-down apoptosis. On the other hand, STAT1 is a tumour suppressor gene and its inactivation contributes to malignant transformation. Initially STAT proteins were extensively studied in leukaemias, but later their role in the development of different solid tumours has been also shown. Aside from their role in the development of tumours, STAT1, STAT3 and STAT5 can be considered as molecular markers for early detection of certain types of tumours, as well as prognostic factors in the determination of tumour aggressiveness and predictors of response to various types of therapy. Evidence of the deregulation of STAT signalling pathway can serve as a basis for designing novel targeted molecular therapeutic strategies that carry a great potential in the therapy of solid tumours and leukaemias.