Treating a Dysregulated JAK/STAT Pathway in Cancer Cells

Abstract

The JAK/STAT pathway is induced by the binding of a cytokine to its cognate receptor. The receptor’s engagement with the cytokine recruits a JAK protein, which activates itself via auto/trans-phosphorylation. In turn, the activated JAKs recruit and phosphorylate STAT proteins. The phosphorylated STAT proteins form a dimer, translocate to the cell nucleus and acts as a transcription factor to induce gene expression. In this way, the JAK/STAT pathway can mediate a cell’s response to extracellular signals. The proteins ultimately induced by the JAK/STAT pathway contribute to processes such as inflammatory response, differentiation, proliferation, and apoptosis. When the JAK/STAT pathway becomes dysregulated, proto-oncogenes and/or tumor-suppressor genes are often inappropriately expressed, commonly resulting in oncogenesis. This review discusses how SOCS, PIAS, and PTPS proteins modulate the JAK/STAT pathway ensuring that it remains cyclic and transient. The use of jakibins, STAT inhibitors, decoy oligonucleotides, RNA interference and genome editing to synthetically regulate a dysregulated JAK/STAT pathway in cancer cells are also considered.