title: Role of Lgr5-positive cells in colorectal cancer.
abstract: The molecular regulation of the growth of colorectal cancer (CRC) cells is not completely understood. Here, we report expression of Lgr5, a stem cell marker for the intestine and hair follicle, in some of the CRC cells in the patients. To determine the role of Lgr5-positive cells in the tumorigenesis of CRCs, we prepared an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA). Transduction of several CRC cell lines with this virus selectively killed Lgr5-positive cells, resulting in significant inhibition of the CRC cell growth in vitro and in vivo. Thus, our data highlight a potential role of Lgr5-positive cells in the tumorigenesis of CRCs, and suggest that treating these Lgr5-positive cells in CRCs may substantially improve the outcome of CRC therapy.
authors.affiliation: Department of Oncology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.
authors.forename: Honghua
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Radiation Oncology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. wangchungang_12@163.com.
authors.forename: Chungang
authors.initials: C
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D000229:Dependovirus / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Colorectal cancer; Diphtheria toxin fragment A (DTA); Lgr5; Tumorigenesis
references.citation: Science. 2012 Aug 10;337(6095):730-5
references.pmid: 22855427
references.citation: Oncogene. 2012 Jun 21;31(25):3009-22
references.pmid: 22002312
references.citation: Diabetologia. 2015 Feb;58(2):313-23
references.pmid: 25338552
references.citation: Oncogene. 2013 Aug 8;32(32):3732-43
references.pmid: 22945646
references.citation: Nat Commun. 2014;5:3150
references.pmid: 24452072
references.citation: Int J Cancer. 2008 Feb 15;122(4):761-8
references.pmid: 17955491
references.citation: Nature. 2007 Oct 25;449(7165):1003-7
references.pmid: 17934449
references.citation: Dev Biol. 2014 Jun 15;390(2):181-90
references.pmid: 24680895
references.citation: Gene Ther. 2008 Jun;15(11):858-63
references.pmid: 18418415
references.citation: J Natl Cancer Inst. 1975 Sep;55(3):555-60
references.pmid: 1159834
references.citation: Acta Histochem. 2013 May;115(4):320-9
references.pmid: 23098761
references.citation: Nat Protoc. 2014 Dec;9(12):2719-24
references.pmid: 25356582
references.citation: Nat Rev Cancer. 2003 Jun;3(6):434-43
references.pmid: 12778133
references.citation: Int J Colorectal Dis. 2010 May;25(5):583-90
references.pmid: 20195621
references.citation: ScientificWorldJournal. 2008 Nov 23;8:1168-76
references.pmid: 19030762
references.citation: Nat Rev Clin Oncol. 2011 Feb 15;8(4):222-32
references.pmid: 21321566
references.citation: Hum Gene Ther. 2004 Apr;15(4):405-13
references.pmid: 15053865
references.citation: Ann Oncol. 2005 May;16 Suppl 4:iv37-43
references.pmid: 15923427
references.citation: Anticancer Res. 2011 Jan;31(1):263-70
references.pmid: 21273608
references.citation: Nat Protoc. 2007;2(3):523-31
references.pmid: 17406616
references.citation: Nat Protoc. 2011 Apr;6(4):482-501
references.pmid: 21455185
references.citation: Curr Med Chem. 2012;19(35):5984-92
references.pmid: 22963565
references.citation: Nat Genet. 2008 Nov;40(11):1291-9
references.pmid: 18849992
references.citation: Histochem Cell Biol. 2014 Dec;142(6):685-91
references.pmid: 25028343
references.citation: Nat Rev Gastroenterol Hepatol. 2013 Feb;10(2):69-70
references.pmid: 23296243
references.citation: PLoS One. 2014 May 02;9(5):e96204
references.pmid: 24787690
references.citation: Am J Pathol. 2009 Mar;174(3):715-21
references.pmid: 19197002
references.citation: Development. 2011 Nov;138(22):4843-52
references.pmid: 22028024
references.citation: Nat Protoc. 2006;1(3):1412-28
references.pmid: 17406430
references.citation: J Gene Med. 2008 Jul;10(7):717-33
references.pmid: 18452237