4.6 Review

Amphiregulin

Journal

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 28, Issue -, Pages 31-41

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2014.01.005

Keywords

Amphiregulin; Epidermal growth factor receptor (EGFR); Cell signaling; Proliferation; Survival; Cancer; Chemoresistance

Funding

  1. FIMA
  2. UTE project CIMA [RTICC-RD06 00200061]
  3. CIBEREhd
  4. FIS from Instituto de Salud Carlos III, Spain [PI10/02642, PI10/00038, PI13/00385, PI13/00359]

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Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR), a widely expressed transmembrane tyrosine kinase. AREG is synthesized as a membrane-anchored precursor protein that can engage in juxtacrine signaling on adjacent cells. Alternatively, after proteolytic processing by cell membrane proteases, mainly TACE/ADAM17, AREG is secreted and behaves as an autocrine or paracrine factor. AREG gene expression and release is induced by a plethora of stimuli including inflammatory lipids, cytokines, hormones, growth factors and xenobiotics. Through EGFR binding AREG activates major intracellular signaling cascades governing cell survival, proliferation and motility. Physiologically, AREG plays an important role in the development and maturation of mammary glands, bone tissue and oocytes. Chronic elevation of AREG expression is increasingly associated with different pathological conditions, mostly of inflammatory and/or neoplastic nature. Here we review the essential aspects of AREG structure, function and regulation, discuss the basis for its differential role within the EGFR family of ligands, and identify emerging aspects in AREG research with translational potential. (C) 2014 Elsevier Ltd. All rights reserved.

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