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Int J Mol Sci. 2019 Jan 29;20(3). pii: E581. doi: 10.3390/ijms20030581.

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

Moon H1,2, Cho K3,4, Shin S5,6, Kim DY7,8, Han KH9,10, Ro SW11,12.

Author information

1
Yonsei Liver Center, Yonsei University College of Medicine, Seoul 03722, Korea. hmoon@yuhs.ac.
2
Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul 03722, Korea. hmoon@yuhs.ac.
3
Yonsei Liver Center, Yonsei University College of Medicine, Seoul 03722, Korea. kyungjoo89@yuhs.ac.
4
Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul 03722, Korea. kyungjoo89@yuhs.ac.
5
Yonsei Liver Center, Yonsei University College of Medicine, Seoul 03722, Korea. SOONYOUNG94@yuhs.ac.
6
Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul 03722, Korea. SOONYOUNG94@yuhs.ac.
7
Yonsei Liver Center, Yonsei University College of Medicine, Seoul 03722, Korea. DYK1025@yuhs.ac.
8
Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea. DYK1025@yuhs.ac.
9
Yonsei Liver Center, Yonsei University College of Medicine, Seoul 03722, Korea. GIHANKHYS@yuhs.ac.
10
Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea. GIHANKHYS@yuhs.ac.
11
Yonsei Liver Center, Yonsei University College of Medicine, Seoul 03722, Korea. simonr@yuhs.ac.
12
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea. simonr@yuhs.ac.

Abstract

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

PMID:
30700007
PMCID:
PMC6387126
DOI:
10.3390/ijms20030581
[Indexed for MEDLINE]
Free PMC Article

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