Review: The JAK/STAT Protein Activation – Role in Cancer Development and Targeted Therapy

Daria      Domanska; Ewa      Brzezianska

doi:10.2174/157436212802481619

Abstract

Signal transducer and activator of transcription (STAT) proteins are second messengers in the JAK/STAT signaling pathway. The activation mechanism of STAT proteins involves phosphorylation on a single tyrosine residue by Janus-activated family kinases (JAK) in response to the binding of a series of extracellular proteins, such as cytokines, growth factors, hormones and membrane receptors. Activated via phosphorylation, STATs dissociate from the receptor, undergo dimerization and translocate to the nucleus, where they induce the transcription of target genes, commonly referred to as Interferon stimulated genes (ISGs). The family of STAT proteins has been documented to participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis and angiogenesis. Constitutively activated STATs are involved in an aberrant signaling pathway which has transforming properties and occurs in cancer development. This review describes the mechanisms of JAK/STAT activation in normal and cancer cells. Moreover, it outlines the role of the JAK/STAT pathway in the inflammatory process as well as in oncogenesis. Additionally, the contribution of STAT and JAK proteins in molecular targeted cancer therapy is discussed.

Keywords: STAT proteins, JAK/STAT signaling pathway, inflammation, targeted therapy, cancer development, dimerization, phosphorylation, oligomerization, β-isoform, docking site