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High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway


High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway

Hyuk Moon et al. Int J Mol Sci.


Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, making up about 80% of cases. Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for HCC. A fibrotic liver typically shows persistent hepatocyte death and compensatory regeneration, chronic inflammation, and an increase in reactive oxygen species, which collaboratively create a tumor-promoting microenvironment via inducing genetic alterations and chromosomal instability, and activating various oncogenic molecular signaling pathways. In this article, we review recent advances in fields of liver fibrosis and carcinogenesis, and consider several molecular signaling pathways that promote hepato-carcinogenesis under the microenvironment of liver fibrosis. In particular, we pay attention to emerging roles of the Hippo-YAP/TAZ signaling pathway in stromal activation, hepatic fibrosis, and liver cancer.

Keywords: cirrhosis; cytokines; genetic instability; hepatocellular carcinoma; inflammation; reactive oxygen species; regeneration.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
Schematic illustration of the mechanistic links between liver fibrosis and cancer. Persistent liver damage caused by viral infection, alcohol, fat, etc. lead to chronic inflammation and activation of various molecular signaling pathways, which contribute to both fibrogenesis and carcinogensis.
Figure 2
Figure 2
Schematic illustration of the roles of YAP/TAZ signaling in hepatic fibrosis and cancer.

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