STAT Signaling in Cancer Prevention

Abstract

Members of the signal transducer and activator of transcription (STAT) family of transcription factors are potential targets for the treatment and prevention of cancers. STAT proteins can be phosphorylated and activated by diverse upstream kinases including cytokine receptors and tyrosine kinases. STATs have been associated with inflammation, cellular transformation, survival, proliferation, invasion, angiogenesis, and metastasis of cancer. Various types of carcinogens, growth factors, oncogenes, radiation, viruses, and inflammatory cytokines have been found to activate STATs. Most STATs are constitutively active in cancer cells but not in normal cells. Phosphorylation of STATs causes dimerization, nuclear translocation, DNA binding, and gene transcription. STATs regulate the expression of genes that mediate cell survival, proliferation, invasion, and angiogenesis. STATs activation has also been associated with both radioresistance and chemoresistance. Furthermore, STATs have been shown to interact, directly or indirectly, with other transcription factors such as hypoxia-inducible factor-1, nuclear factor-kappa B, and peroxisome proliferator activated receptor-gamma. Several small molecule inhibitors, peptides and natural products are being developed for the prevention and treatment of cancer. Some chemopreventive agents have been shown to inhibit the IL6R-JAK/STAT pathway that is crucial for cell proliferation, survival, and inflammation. This suggests that chemopreventive agents might be candidates for cancer prevention because they reduce inflammation and prevent tumor growth, metastasis and angiogenesis. This review discusses the roles of various STATs in cancer prevention.