Abstract
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.
Highlights
Plasminogen Activator Inhibitor-1 (PAI-1) Plays a Major Role in Regulating Protein Synthesis and Wound Healing Process
These results provide strong evidence that increased PAI-1 in liver disease may further exacerbate the progression to Hepatocellular carcinoma (HCC) by engaging in differentiation of the cancer stem-like cells (CSC) phenotype
Recent studies have identified the role of the CSC as well as their specific markers in the liver disease progression [11], and further on it has been confirmed that increased CSC properties increased epithelialmesenchymal transition (EMT) from HCVinfected hepatocytes [13,14,15]
Summary
Plasminogen Activator Inhibitor-1 (PAI-1) Plays a Major Role in Regulating Protein Synthesis and Wound Healing Process. Sustained PAI-1 activity induces excessive accumulation of proteins which leads to an epithelialmesenchymal transition (EMT) state as well as an increase in cell invasiveness that contributes to fibrosis (Figure 1B). PAI-1, involved in collagen synthesis and ECM protein homeostasis, has been suggested as biomarker and a potential therapeutic target in the progression of fibrotic diseases, including cirrhosis and HCC.
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