The multiple roles of amphiregulin in human cancer

Biochim Biophys Acta. 2011 Dec;1816(2):119-31. doi: 10.1016/j.bbcan.2011.05.003. Epub 2011 May 30.

Abstract

Amphiregulin (AREG) is one of the ligands of the epidermal growth factor receptor (EGFR). AREG plays a central role in mammary gland development and branching morphogenesis in organs and is expressed both in physiological and in cancerous tissues. Various studies have highlighted the functional role of AREG in several aspects of tumorigenesis, including self-sufficiency in generating growth signals, limitless replicative potential, tissue invasion and metastasis, angiogenesis, and resistance to apoptosis. The oncogenic activity of AREG has already been described in the most common human epithelial malignancies, such as lung, breast, colorectal, ovary and prostate carcinomas, as well as in some hematological and mesenchymal cancers. Furthermore, AREG is also involved in resistance to several cancer treatments. In this review, we describe the various roles of AREG in oncogenesis and discuss its translational potential, such as the development of anti-AREG treatments, based on AREG activity. In the last decade, independent groups have reported successful but sometimes contradictory results in relation to the potential of AREG to serve as a prognostic and/or predictive marker for oncology, especially with regard to anti-EGFR therapies. Thus, we also discuss the potential usefulness of using AREG as a therapeutic target and validated biomarker for predicting cancer outcomes or treatment efficacy.

Publication types

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

MeSH terms

  • Amphiregulin
  • Animals
  • Drug Resistance, Neoplasm
  • EGF Family of Proteins
  • ErbB Receptors / physiology
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / chemistry
  • Glycoproteins / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / etiology*
  • Prognosis

Substances

  • AREG protein, human
  • Amphiregulin
  • EGF Family of Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • ErbB Receptors