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

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...

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Bibliographic Details
Published in:Journal of gastroenterology 2014, Vol.49 (1), p.9-23
Main Authors: Berasain, Carmen, Avila, Matías A.
Format: Article
Language:English
Subjects:
Abdominal Surgery
Antineoplastic Agents - pharmacology
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Cell Transformation, Neoplastic - metabolism
Colorectal Surgery
Epidermal growth factor
Gastroenterology
Hepatology
Humans
Liver - metabolism
Liver Cirrhosis - metabolism
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Liver Regeneration - physiology
Medicine
Medicine & Public Health
Molecular Targeted Therapy - methods
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - physiology
Review
Signal Transduction - physiology
Surgical Oncology
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Summary: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.
ISSN:0944-1174
1435-5922
DOI:10.1007/s00535-013-0907-x