Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review)

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a primary malignant liver tumour whose incidence is second only to that of hepatocellular carcinoma. ICC is a highly heterogeneous disease arising from neoplastic transformation of intrahepatic biliary epithelial cells (cholangiocytes), and it is characterized by a very poor prognosis. Signal transducer and activator of transcription 3 (STAT3) is an important oncogene that is widely expressed in numerous cancers. STAT3 is a candidate target for the treatment of ICC. However, studies on STAT3 and the occurrence and development of ICC require improvements. Therefore, the present review summarized the mechanism of STAT3 in ICC and provided a theoretical basis for STAT3 to become an effective target for determining the prognosis and treatment of ICC.

Keywords: intrahepatic cholangiocarcinoma; signal transducer and activator of transcription 3.

Figure 1.

Structure of the STAT3 protein. STAT3, signal transducer and activator of transcription 3.

Figure 2.

STAT3 is involved in signal transduction pathways associated with intrahepatic cholangiocarcinoma; STAT3 is activated by the cytokine IL-6 and other growth factors, including EGFR, fibroblast growth factor receptor and platelet-derived growth factor receptor, through tyrosine phosphorylation. After dimerization, STAT3 translocates into the nucleus, where it induces gene transcription. STAT3 signalling mediates cell growth, proliferation, inflammatory cytokine production, cell invasion and migration. STAT3, signal transducer and activator of transcription 3; IL, interleukin; EGFR, epidermal growth factor receptor.

Figure 3.

STAT3-associated target proteins in intrahepatic cholangiocarcinoma and numerous domain-specific inhibitors have also been identified. STAT3, signal transducer and activator of transcription 3.