Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 21, 2012; 18(31): 4071-4081
Published online Aug 21, 2012. doi: 10.3748/wjg.v18.i31.4071
Inflammation- and stress-related signaling pathways in hepatocarcinogenesis
Hayato Nakagawa, Shin Maeda
Hayato Nakagawa, Department of Gastroenterology, University of Tokyo, Tokyo 113-8655, Japan
Shin Maeda, Department of Gastroenterology, Yokohama City University, Yokohama 236-0004, Japan
Author contributions: Nakagawa H drafted of the article; Maeda S was contributed to the critical revision of the manuscript.
Supported by A fellowship from the Daiichi Sankyo Foundation of Life Science, to Nakagawa H
Correspondence to: Shin Maeda, Professor, Department of Gastroenterology, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. smaeda@med.yokohama-cu.ac.jp
Telephone: +81-45-7872326 Fax: +81-45-7872327
Received: February 15, 2012
Revised: May 28, 2012
Accepted: June 8, 2012
Published online: August 21, 2012

It has been established that cancer can be promoted and exacerbated by inflammation. Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and its long-term prognosis remains poor. Although HCC is a complex and heterogeneous tumor with several genomic mutations, it usually develops in the context of chronic liver damage and inflammation, suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC. Chronic liver damage induces a persistent cycle of necro-inflammation and hepatocyte regeneration, resulting in genetic mutations in hepatocytes and expansion of initiated cells, eventually leading to HCC development. Recently, several inflammation- and stress-related signaling pathways have been identified as key players in these processes, which include the nuclear factor-κB, signal transducer and activator of transcription, and stress-activated mitogen- activated protein kinase pathways. Although these pathways may suggest potential therapeutic targets, they have a wide range of functions and complex crosstalk occurs among them. This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis.

Keywords: Hepatocellular carcinoma, Inflammation, Nuclear factor-κB, Mitogen-activated protein kinase, Signal transducer and activator of transcription, c-Jun NH2-terminal kinase, p38, Transforming growth factor-activated kinase 1, Apoptosis signal-regulating kinase 1