The EGFR signalling system in the liver: from hepatoprotection to hepatocarcinogenesis

J Gastroenterol. 2014 Jan;49(1):9-23. doi: 10.1007/s00535-013-0907-x. Epub 2013 Dec 10.


The liver displays an outstanding wound healing and regenerative capacity unmatched by any other organ. This reparative response is governed by a complex network of inflammatory mediators, growth factors and metabolites that are set in motion in response to hepatocellular injury. However, when liver injury is chronic, these regenerative mechanisms become dysregulated, facilitating the accumulation of genetic alterations leading to unrestrained cell proliferation and the development of hepatocellular carcinoma (HCC). The epidermal growth factor receptor (EGFR or ErbB1) signaling system has been identified as a key player in all stages of the liver response to injury, from early inflammation and hepatocellular proliferation to fibrogenesis and neoplastic transformation. The EGFR system engages in extensive crosstalk with other signaling pathways, acting as a true signaling hub for other growth factors, cytokines and inflammatory mediators. Here, we briefly review essential aspects of the biology of the EGFR, the other ErbB receptors, and their ligands in liver injury, regeneration and HCC development. Some aspects of the preclinical and clinical experience with EGFR therapeutic targeting in HCC are also discussed.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Transformation, Neoplastic / metabolism*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / physiology*
  • Humans
  • Liver / metabolism*
  • Liver Cirrhosis / metabolism
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Liver Regeneration / physiology
  • Molecular Targeted Therapy / methods
  • Signal Transduction / physiology


  • Antineoplastic Agents
  • ErbB Receptors