JAK-STAT Signaling in Autoimmunity and Cancer

Abstract

The JAK-STAT pathway is an essential cell survival signaling that regulates gene expressions related to inflammation, immunity and cancer. Cytokine receptors, signal transducer and activator of transcription (STAT) proteins, and Janus kinases (JAKs) are the critical component of this signaling cascade. When JAKs are stimulated by cytokines, STAT phosphorylation, dimerization, and nuclear translocation occur, which eventually impacts gene transcription. Dysregulation of JAK-STAT signaling is linked with various autoimmune diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. This pathway is constitutively activated in human malignancies and leads to tumor cell survival, proliferation, and immune evasion. Oncogenic mutations in the JAK and STAT genes have been found in solid tumors, leukemia, and lymphoma. Targeting the JAK-STAT pathway is a viable and promising therapeutic strategy for the treatment of autoimmune diseases and cancers.