STAT3: a multifaceted oncoprotein

Signal transducer and activator of transcription (STAT) 3 is a key signalling protein engaged by a multitude of growth factors and cytokines to elicit diverse biological outcomes including cellular growth, differentiation, and survival. The complete loss of STAT3 is not compatible with life and even partial loss of function mutations lead to debilitating pathologies like hyper IgE syndrome. Conversely, augmented STAT3 activity has been reported in as many as 50% of all human tumours. The dogma of STAT3 activity posits that it is a tyrosine phosphorylated transcription factor which modulates the expression of hundreds of genes. However, the regulation and biological consequences of STAT3 activation are far more complex. In addition to tyrosine phosphorylation, STAT3 is decorated with a plethora of post-translational modifications which regulate STAT3's nuclear function in addition to its non-genomic activities. In addition to these emerging complexities in the biochemical regulation of STAT3 activity, recent studies reveal that STAT3 is either oncogenic or a tumour suppressor. This review will explore these complexities.