JAK/STAT signaling pathways and cancer. Janus kinases/signal transducers and activators of transcription.

Recent highlights in understanding molecular nature of signaling pathways that mediate biological effects of various external stimuli and control number of normal physiological processes of cells such as growth, differentiation, senescence and apoptosis, defined three major groups of proteins which apparently play an essential role in transmitting external signals from surface membrane to target genes in the nucleus. These include Janus kinases (JAKs), signal transducers and activators of transcription (STATs) and their endogenous inhibitors of SOCS family. Their inappropriate functioning and defective cross-talking associate with several human disorders including cancer. There is an increasing evidence that perturbances in STAT proteins are involved in the pathogenesis of some human malignancies. Moreover, cancer-related defective JAK/STAT/SOCS pathways may negatively affect tumor response to the cytokine-based immunotherapy. This article provides an overview of the current knowledge about JAK/STAT/SOCS intracellular signaling cascades with special emphasis on their abnormalities in cancer.