Role of STAT3 in Liver Cancer

Abstract

Hepatocellular carcinoma (HCC) is a malignant cancer that shows heterogeneous etiology and the third leading of cancer-related deaths in the world. In spite of its severity, there is only one systemic chemotherapy drug known as sorafenib showing a valuable effect on a small number of HCC patients. Signal transducers and activators of transcription (STATs), a family of transcription factors, consist of seven members in mammalian cells: STATs 1, 2, 3, 4, 5a, 5b, and 6. STAT transcription factors have a characteristic Src homology 2 (SH2) domain whose function is indispensable to the activation of STAT proteins triggered by Janus kinase (JAK) signaling. Among the STAT transcription factor family, STAT3 performs a vital function in advancement and tumorigenesis because it participates in replicating various proteins that are responsible for angiogenesis, proliferation, invasion, metastasis, and apoptosis. Although the activation of STAT3 is usually transient in normal cells, cancer cells show a positive feed-forward loop that results in the persistent activation of STAT3. The expression and activity of STAT3 are increased in a wide range of malignancies. Although several studies have reported the oncogenic functions, the antitumor effects of STAT3 should be considered carefully in the development of therapeutic methods that target STAT3 signaling. We believe that STAT3 signaling will be a promising target of treatment for HCC patients who need further research of adverse effects or personalized treatment via the modulation of STAT3 signaling.