Inflammation- and stress-related signaling pathways in hepatocarcinogenesis

World J Gastroenterol. 2012 Aug 21;18(31):4071-81. doi: 10.3748/wjg.v18.i31.4071.


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

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Hepatocellular / physiopathology*
  • Cytokines / physiology
  • Humans
  • Inflammation / physiopathology*
  • Liver Neoplasms / physiopathology*
  • Mitogen-Activated Protein Kinase Kinases / physiology
  • NF-kappa B / physiology
  • STAT Transcription Factors / physiology
  • Signal Transduction / physiology*
  • Stress, Physiological / physiology*


  • Cytokines
  • NF-kappa B
  • STAT Transcription Factors
  • Mitogen-Activated Protein Kinase Kinases