PMID- 24463227 OWN - NLM STAT- MEDLINE DCOM- 20150226 LR - 20220310 IS - 1096-3634 (Electronic) IS - 1084-9521 (Linking) VI - 28 DP - 2014 Apr TI - Amphiregulin. PG - 31-41 LID - S1084-9521(14)00006-8 [pii] LID - 10.1016/j.semcdb.2014.01.005 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Berasain, Carmen AU - Berasain C AD - Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Avda. Pio XII, n55, 31008 Pamplona, Spain; CIBERehd, Clinica Universidad de Navarra, Avda. Pio XII, n55, 31008 Pamplona, Spain. Electronic address: cberasain@unav.es. FAU - Avila, Matias A AU - Avila MA AD - Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Avda. Pio XII, n55, 31008 Pamplona, Spain; CIBERehd, Clinica Universidad de Navarra, Avda. Pio XII, n55, 31008 Pamplona, Spain. Electronic address: maavila@unav.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140123 PL - England TA - Semin Cell Dev Biol JT - Seminars in cell & developmental biology JID - 9607332 RN - 0 (Amphiregulin) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Amphiregulin/genetics/*metabolism MH - Animals MH - Cell Proliferation/*physiology MH - ErbB Receptors/*metabolism MH - Humans MH - Neoplasms/metabolism MH - Signal Transduction/*physiology OTO - NOTNLM OT - Amphiregulin OT - Cancer OT - Cell signaling OT - Chemoresistance OT - Epidermal growth factor receptor (EGFR) OT - Proliferation OT - Survival EDAT- 2014/01/28 06:00 MHDA- 2015/02/27 06:00 CRDT- 2014/01/28 06:00 PHST- 2013/12/04 00:00 [received] PHST- 2014/01/10 00:00 [revised] PHST- 2014/01/14 00:00 [accepted] PHST- 2014/01/28 06:00 [entrez] PHST- 2014/01/28 06:00 [pubmed] PHST- 2015/02/27 06:00 [medline] AID - S1084-9521(14)00006-8 [pii] AID - 10.1016/j.semcdb.2014.01.005 [doi] PST - ppublish SO - Semin Cell Dev Biol. 2014 Apr;28:31-41. doi: 10.1016/j.semcdb.2014.01.005. Epub 2014 Jan 23.