Disruption of the crypt niche promotes outgrowth of mutated colorectal tumor stem cells.
Adult stem cells
Colorectal cancer
Oncology
Stem cells
Tight junctions
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
09
08
2021
accepted:
26
01
2022
entrez:
9
3
2022
pubmed:
10
3
2022
medline:
12
4
2022
Statut:
epublish
Résumé
Recent data establish a logarithmic expansion of leucine rich repeat containing G protein coupled receptor 5-positive (Lgr5+) colonic epithelial stem cells (CESCs) in human colorectal cancer (CRC). Complementary studies using the murine 2-stage azoxymethane-dextran sulfate sodium (AOM-DSS) colitis-associated tumor model indicate early acquisition of Wnt pathway mutations drives CESC expansion during adenoma progression. Here, subdivision of the AOM-DSS model into in vivo and in vitro stages revealed DSS induced physical separation of CESCs from stem cell niche cells and basal lamina, a source of Wnt signals, within hours, disabling the stem cell program. While AOM delivery in vivo under non-adenoma-forming conditions yielded phenotypically normal mucosa and organoids derived thereof, niche injury ex vivo by progressive DSS dose escalation facilitated outgrowth of Wnt-independent dysplastic organoids. These organoids contained 10-fold increased Lgr5+ CESCs with gain-of-function Wnt mutations orthologous to human CRC driver mutations. We posit CRC originates by niche injury-induced outgrowth of normally suppressed mutated stem cells, consistent with models of adaptive oncogenesis.
Identifiants
pubmed: 35260534
pii: 153793
doi: 10.1172/jci.insight.153793
pmc: PMC8983138
doi:
pii:
Substances chimiques
Azoxymethane
MO0N1J0SEN
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Références
Nat Rev Genet. 2016 May;17(5):284-99
pubmed: 26972587
Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5399-407
pubmed: 27573849
Gastroenterology. 2011 Nov;141(5):1762-72
pubmed: 21889923
Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G7-17
pubmed: 15194558
Genes Chromosomes Cancer. 2005 Mar;42(3):238-46
pubmed: 15609344
Virchows Arch A Pathol Anat Histopathol. 1988;413(6):499-504
pubmed: 3144085
Nature. 2013 Feb 14;494(7436):247-50
pubmed: 23354049
Nat Rev Mol Cell Biol. 2008 Aug;9(8):628-38
pubmed: 18628784
Cell. 1996 Oct 18;87(2):159-70
pubmed: 8861899
Cell. 2004 Aug 6;118(3):285-96
pubmed: 15294155
Int J Radiat Biol. 2003 Feb;79(2):71-81
pubmed: 12569011
Nature. 2011 Jun 15;474(7351):318-26
pubmed: 21677748
Cancer Sci. 2004 Jun;95(6):475-80
pubmed: 15182426
Nat Cell Biol. 2017 Jul;19(7):774-786
pubmed: 28581476
J Radiat Res. 2013 Nov 1;54(6):1161-3
pubmed: 23732771
Nature. 2009 May 14;459(7244):262-5
pubmed: 19329995
Nature. 2018 Jun;558(7710):449-453
pubmed: 29875413
Gastroenterology. 2016 Apr;150(4):808-10
pubmed: 26924087
Cancer Cell. 2009 Feb 3;15(2):91-102
pubmed: 19185844
Sci Rep. 2015 Dec 17;5:18521
pubmed: 26673743
Clin Cancer Res. 2004 Feb 15;10(4):1401-8
pubmed: 14977843
Nature. 2009 Jan 29;457(7229):608-11
pubmed: 19092804
Nat Immunol. 2017 Jul 19;18(8):843-850
pubmed: 28722707
J Carcinog. 2011 Mar 24;10:9
pubmed: 21483655
Cell. 2002 Oct 18;111(2):241-50
pubmed: 12408868
Pathology. 2018 Jan;50(1):49-59
pubmed: 29169633
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21635-40
pubmed: 21118981
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1565-70
pubmed: 20080688
Nat Genet. 2015 Jun;47(6):668-71
pubmed: 25938944
Gastroenterology. 2012 Nov;143(5):1266-1276
pubmed: 22841781
Carcinogenesis. 2000 Nov;21(11):1935-40
pubmed: 11062151
Carcinogenesis. 2014 Apr;35(4):849-58
pubmed: 24282287
Cancer Res. 2020 Mar 1;80(5):927-928
pubmed: 32122905
Genesis. 2007 Sep;45(9):593-605
pubmed: 17868096
Cancer Cell. 2009 Feb 3;15(2):103-13
pubmed: 19185845
J Clin Invest. 2005 Jul;115(7):1765-76
pubmed: 15965503
Nat Commun. 2013;4:2610
pubmed: 24162018
Radiat Res. 1960 Oct;13:556-93
pubmed: 13726391
Gastroenterology. 2011 May;140(6):1807-16
pubmed: 21530747
Gut. 2017 Apr;66(4):683-691
pubmed: 26818619
Med Pharm Rep. 2019 Jul;92(3):246-252
pubmed: 31460505
Curr Protoc Stem Cell Biol. 2010 May;Chapter 5:Unit5A.4
pubmed: 20443207
PLoS One. 2013 May 14;8(5):e63298
pubmed: 23691015
Acta Pharmacol Sin. 2007 Sep;28(9):1450-9
pubmed: 17723178
J Biol Chem. 2017 May 26;292(21):8569-8576
pubmed: 28389557
Science. 2012 Aug 10;337(6095):730-5
pubmed: 22855427
Gastroenterology. 2012 May;142(5):1195-1205.e6
pubmed: 22333952
Int J Oncol. 2003 Jan;22(1):145-50
pubmed: 12469197
World J Gastroenterol. 2008 Jun 28;14(24):3866-71
pubmed: 18609711
J Surg Res. 2007 Jun 1;140(1):12-9
pubmed: 17418867
Blood. 2018 Sep 20;132(12):1265-1278
pubmed: 30064973
Drug Discov Today. 2015 Dec;20(12):1422-8
pubmed: 26320725
Cell. 2012 Jun 8;149(6):1192-205
pubmed: 22682243
Genome Res. 2015 May;25(5):714-24
pubmed: 25858951
Cell Signal. 2018 Jan;42:97-105
pubmed: 28958617
Cancer Res. 2020 Mar 1;80(5):1219-1227
pubmed: 31690670
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10779-84
pubmed: 8855257
Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11127-32
pubmed: 23776211
Cell Stem Cell. 2017 Feb 2;20(2):177-190.e4
pubmed: 27939219
Biostatistics. 2004 Oct;5(4):557-72
pubmed: 15475419
Nat Rev Immunol. 2009 Nov;9(11):799-809
pubmed: 19855405
Nature. 2007 Oct 25;449(7165):1003-7
pubmed: 17934449
Nature. 2011 Jan 20;469(7330):415-8
pubmed: 21113151
Gut. 2019 Mar;68(3):547-561
pubmed: 30297438
Nat Rev Cancer. 2013 Nov;13(11):759-71
pubmed: 24154716
Science. 2013 Jun 7;340(6137):1190-4
pubmed: 23744940
Gastroenterology. 2012 Dec;143(6):1518-1529.e7
pubmed: 22922422
Carcinogenesis. 2000 Jun;21(6):1117-20
pubmed: 10836998
Nature. 2012 Jul 18;487(7407):330-7
pubmed: 22810696
J Biomed Biotechnol. 2012;2012:718617
pubmed: 22665990
Cancer Sci. 2003 Nov;94(11):965-73
pubmed: 14611673
Elife. 2019 Apr 29;8:
pubmed: 31034356
Biochim Biophys Acta. 2013 Aug;1836(1):80-9
pubmed: 23333833
Semin Immunopathol. 2013 Mar;35(2):229-44
pubmed: 23161445
Methods Mol Biol. 2015;1267:125-44
pubmed: 25636467
Trends Cancer. 2016 Oct;2(10):552-560
pubmed: 28439564
Cancer Res. 1978 Dec;38(12):4427-30
pubmed: 719628
Gastroenterology. 2007 Feb;132(2):628-32
pubmed: 17320548
Nat Med. 2012 Mar 11;18(4):618-23
pubmed: 22406745
Inflamm Bowel Dis. 2015 Feb;21(2):409-18
pubmed: 25563695
Crit Rev Toxicol. 2002 Sep;32(5):413-44
pubmed: 12389870
World J Gastroenterol. 2017 Sep 7;23(33):6016-6029
pubmed: 28970718
Gastroenterology. 2016 Apr;150(4):931-43
pubmed: 26764183
Gastroenterology. 2007 Dec;133(6):1869-81
pubmed: 18054559
Cancer Lett. 2004 Apr 8;206(2):193-9
pubmed: 15013524
BMC Cancer. 2016 Jan 12;16:12
pubmed: 26758198
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8683-8
pubmed: 12072559
Cell. 2017 Jun 1;169(6):985-999
pubmed: 28575679
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821