title: LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor.
abstract: In baseball parlance, a triple threat is a person who can run, hit and throw with aplomb. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a cell surface protein that antagonises ERBB receptor signalling by downregulating receptor levels. Over 10 years ago, Hedman et al postulated that LRIG1 might be a tumour suppressor. Recently, Powell et al provided in vivo evidence substantiating that claim by demonstrating that Lrig1 loss in mice leads to spontaneously arising, highly penetrant intestinal adenomas. Interestingly, Lrig1 also marks stem cells in the gut, suggesting a potential role for Lrig1 in maintaining intestinal epithelial homeostasis. In this review, we will discuss the ability of LRIG1 to act as a triple threat: pan-ERBB negative regulator, intestinal stem cell marker and tumour suppressor. We will summarise studies of LRIG1 expression in human cancers and discuss possible related roles for LRIG2 and LRIG3.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: E J
authors.initials: EJ
authors.lastname: Poulin
authors.forename: R J
authors.initials: RJ
authors.lastname: Coffey
mesh_terms: D000236:Adenoma / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018739:Oncogene Proteins v-erbB / Q000037:antagonists & inhibitors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C484445:LRIG1 protein, human; C488673:LRIG2 protein, human; C496406:LRIG3 protein, human; C101671:Lrig1 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018739:Oncogene Proteins v-erbB; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors
references.citation: Acta Oncol. 2010 Aug;49(6):812-5
references.pmid: 20553099
references.citation: Exp Cell Res. 2011 Feb 15;317(4):504-12
references.pmid: 21087604
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: FEBS Lett. 2002 Jun 19;521(1-3):67-71
references.pmid: 12067728
references.citation: Oncogene. 2008 Sep 25;27(43):5741-52
references.pmid: 18542056
references.citation: Nature. 1998 Nov 12;396(6707):177-80
references.pmid: 9823898
references.citation: Acta Oncol. 2007;46(8):1118-22
references.pmid: 17851870
references.citation: J Neurooncol. 2012 Jul;108(3):435-41
references.pmid: 22484910
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Oct;18(10):2709-16
references.pmid: 19815638
references.citation: Oncogene. 2014 Jan 2;33(1):34-43
references.pmid: 23208509
references.citation: PLoS One. 2010 Dec 07;5(12):e15003
references.pmid: 21170350
references.citation: Nat Cell Biol. 2012 Mar 04;14(4):401-8
references.pmid: 22388892
references.citation: Acta Oncol. 2002;41(4):352-4
references.pmid: 12234026
references.citation: EMBO J. 2004 Aug 18;23(16):3270-81
references.pmid: 15282549
references.citation: Am J Pathol. 2001 Jul;159(1):119-30
references.pmid: 11438460
references.citation: Oncogene. 2007 Jan 18;26(3):368-81
references.pmid: 16847455
references.citation: Int J Gynecol Cancer. 2008 Mar-Apr;18(2):312-7
references.pmid: 17624990
references.citation: BMC Res Notes. 2012 May 03;5:216
references.pmid: 22554477
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2011 Aug;31(4):520
references.pmid: 21823015
references.citation: Int J Cancer. 2011 Jun 15;128(12):2843-52
references.pmid: 21128282
references.citation: Neuro Oncol. 2013 Sep;15(9):1200-11
references.pmid: 23723255
references.citation: Genesis. 2001 Aug;30(4):259-63
references.pmid: 11536432
references.citation: Cell Stem Cell. 2009 May 8;4(5):427-39
references.pmid: 19427292
references.citation: Mol Cell Biol. 2007 Mar;27(5):1934-46
references.pmid: 17178829
references.citation: PLoS One. 2010 Feb 01;5(2):e8981
references.pmid: 20126551
references.citation: J Neurosci. 2008 Jan 2;28(1):39-49
references.pmid: 18171921
references.citation: Cell. 2012 Mar 30;149(1):146-58
references.pmid: 22464327
references.citation: Cancer Lett. 2009 Jun 8;278(1):104-12
references.pmid: 19200647
references.citation: Br J Urol. 1996 Apr;77(4):524-9
references.pmid: 8777611
references.citation: BMC Bioinformatics. 2010 Mar 24;11:150
references.pmid: 20334636
references.citation: Dermatol Surg. 2005 Apr;31(4):423-30
references.pmid: 15871317
references.citation: J Biol Chem. 2004 Nov 5;279(45):47050-6
references.pmid: 15345710
references.citation: PLoS One. 2009 Sep 25;4(9):e7169
references.pmid: 19779621
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2012 Apr;32(2):227-232
references.pmid: 22528225
references.citation: J Biol Chem. 1996 Sep 13;271(37):22522-7
references.pmid: 8798419
references.citation: Development. 2008 Apr;135(7):1283-93
references.pmid: 18287203
references.citation: Neuropathology. 2009 Jun;29(3):242-7
references.pmid: 18992012
references.citation: Cancer Res. 2008 Oct 15;68(20):8286-94
references.pmid: 18922900
references.citation: Development. 2008 Dec;135(24):4091-9
references.pmid: 19004851
references.citation: Mol Cancer Res. 2011 Oct;9(10):1406-17
references.pmid: 21821674
references.citation: Gynecol Oncol. 2009 Jan;112(1):235-40
references.pmid: 18976801