Hepatocellular carcinoma (HCC) is a significant cause of cancer mortality worldwide. Chronic hepatic inflammation and fibrosis play a critical role in the development of HCC. Liver fibrosis develops as a result of response to injury such that a persistent and excessive wound healing response induces extracellular matrix (ECM) deposition leading to HCC. PAI-1 is a fibrinolysis inhibitor involved in regulating protein degradation and homeostasis while assisting wound healing. PAI-1 presents increased levels in various diseases such as fibrosis, cancer, obesity and metabolic syndrome. Moreover, PAI-1 has been extensively studied for developing potential therapies against fibrosis. In the present review, we summarize how PAI-1 affects oncogenesis during liver disease progression based on the recently published literatures. Although there are controversies regarding the role of PAI-1 and approaches to treatment, this review suggests that proper manipulation of PAI-1 activity could provide a novel therapeutic option on the development of chronic liver disease via modulation of cancer stem-like cells (CSCs) differentiation.
Keywords: CSCs; HCC; HCV; Hepatocytes; PAI-1.