schliessen

Filtern

 

Bibliotheken

Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids

Primary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-ter... Full description

Journal Title: Cancer letters 2018-11-01, Vol.436, p.109-118
Main Author: Liu, Xi
Other Authors: Cheng, Yulan , Abraham, John M , Wang, Zhixiong , Wang, Zhe , Ke, Xiquan , Yan, Rong , Shin, Eun Ji , Ngamruengphong, Saowanee , Khashab, Mouen A , Zhang, Guanjun , McNamara, George , Ewald, Andrew J , Lin, DeChen , Liu, Zhengwen , Meltzer, Stephen J
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
Quelle: Alma/SFX Local Collection
Publisher: Ireland: Elsevier B.V
ID: ISSN: 0304-3835
Link: https://www.ncbi.nlm.nih.gov/pubmed/30144514
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_journals_2104693255
title: Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids
format: Article
creator:
  • Liu, Xi
  • Cheng, Yulan
  • Abraham, John M
  • Wang, Zhixiong
  • Wang, Zhe
  • Ke, Xiquan
  • Yan, Rong
  • Shin, Eun Ji
  • Ngamruengphong, Saowanee
  • Khashab, Mouen A
  • Zhang, Guanjun
  • McNamara, George
  • Ewald, Andrew J
  • Lin, DeChen
  • Liu, Zhengwen
  • Meltzer, Stephen J
subjects:
  • Adenocarcinoma
  • Adenomatous polyposis coli
  • Adenomatous Polyposis Coli Protein - genetics
  • Adenomatous Polyposis Coli Protein - metabolism
  • Analysis
  • Apoptosis
  • Apoptosis - genetics
  • Article
  • Barrett esophagus
  • Barrett Esophagus - metabolism
  • Barrett Esophagus - pathology
  • Barrett's esophagus
  • beta Catenin - genetics
  • Cancer
  • Cell activation
  • Cell Differentiation - genetics
  • Cell Movement - genetics
  • Cell Proliferation - genetics
  • Cell Transformation, Neoplastic - genetics
  • Collagen
  • Conflicts of interest
  • CRISPR
  • CRISPR-Cas Systems
  • CRISPR/Cas9
  • Deoxyribonucleic acid
  • DNA
  • DNA methylation
  • Esophagus
  • Gene Editing - methods
  • Gene Knockout Techniques
  • Genomes
  • Genomics
  • Humans
  • Models
  • Models, Genetic
  • Mutation
  • Neoplastic transformation
  • Noise
  • Organoids
  • Organoids - metabolism
  • Organoids - pathology
  • Plasmids
  • Signaling
  • Transformation
  • Tumor cell lines
  • Tumorigenesis
  • Wnt protein
  • Wnt signaling
  • Wnt Signaling Pathway - genetics
  • β-Catenin
ispartof: Cancer letters, 2018-11-01, Vol.436, p.109-118
description: Primary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC-knockout (APCKO) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APCKO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise present in immortalized or cancer-derived cell lines. •A long-term expansion Wnt-activated human BE organoid model has been established using CRISPR-Cas9 combined with a niche-based selection system.•Compared to wild-type BE organoids, Wnt-activated BE organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, overexpression of Ki67, c-myc and cyclin D1, and enhanced protrusive migration ability, which disrupted reorganization and integrity of the basement membrane.•This CRISPR-Cas9 editing human-derived organoid model recapitulates the role of activated Wnt signaling during BE neoplastic transformation.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0304-3835
fulltext: fulltext
issn:
  • 0304-3835
  • 1872-7980
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.6226194
LOCALfalse
PrimoNMBib
record
control
sourceidgale_opena
recordidTN_cdi_proquest_journals_2104693255
sourceformatXML
sourcesystemPC
galeidA554472013
sourcerecordidA554472013
originalsourceidFETCH-LOGICAL-c435t-f776e41d3c6c6205e247b2d927b6ef6980b9c59dc7a49b6d774a4b6588d8bbfb3
addsrcrecordideNp9kV9vFCEUxSdGY9fqNzCGxOdZYYY_My8mdVNtkxpN1fhILnBny2YWVmBN-u1lndpHw00IcM7hwq9pXjO6ZpTJd7u1hTBjWXeUDWtai6knzYoNqmvVONCnzYr2lLf90Iuz5kXOO0qp4Eo8b856yjgXjK-a9Dk6nH3Ykp-hkOy3Af6uzD3Z3F5_-3rbbiCPZIsh7pGg8-V0mtDCwZfjDAUzCRgPM2QPxAdyd9xDIB8gJSyFYFXd1XyYSUxbCNG7_LJ5NsGc8dXDfN78-Hj5fXPV3nz5dL25uGkt70VpJ6UkcuZ6K63sqMCOK9O5sVNG4iTrC81oxeisAj4a6ZTiwI0Uw-AGYybTnzdXS248YACfUB-S30O61xG8dgGLjk53UunBcsqYGkcQgg5oHAXWT46NwgFng6xRb5eoQ4q_jpiL3sVjql-Vdccol2PfCVFV60W1hRm1D1MsCWwdDvfexoCTr_sXQnCuKrS-GvhisCnmnHB67JBRfYKsd3qBrE-QNa3FVLW9eejmaPboHk3_qFbB-0WA9Xt_e0w6W4_BVnyVXNEu-v_f8Ae0Vbjj
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
pqid2104693255
display
typearticle
titleModeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids
sourceAlma/SFX Local Collection
creatorLiu, Xi ; Cheng, Yulan ; Abraham, John M ; Wang, Zhixiong ; Wang, Zhe ; Ke, Xiquan ; Yan, Rong ; Shin, Eun Ji ; Ngamruengphong, Saowanee ; Khashab, Mouen A ; Zhang, Guanjun ; McNamara, George ; Ewald, Andrew J ; Lin, DeChen ; Liu, Zhengwen ; Meltzer, Stephen J
creatorcontribLiu, Xi ; Cheng, Yulan ; Abraham, John M ; Wang, Zhixiong ; Wang, Zhe ; Ke, Xiquan ; Yan, Rong ; Shin, Eun Ji ; Ngamruengphong, Saowanee ; Khashab, Mouen A ; Zhang, Guanjun ; McNamara, George ; Ewald, Andrew J ; Lin, DeChen ; Liu, Zhengwen ; Meltzer, Stephen J
descriptionPrimary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC-knockout (APCKO) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APCKO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise present in immortalized or cancer-derived cell lines. •A long-term expansion Wnt-activated human BE organoid model has been established using CRISPR-Cas9 combined with a niche-based selection system.•Compared to wild-type BE organoids, Wnt-activated BE organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, overexpression of Ki67, c-myc and cyclin D1, and enhanced protrusive migration ability, which disrupted reorganization and integrity of the basement membrane.•This CRISPR-Cas9 editing human-derived organoid model recapitulates the role of activated Wnt signaling during BE neoplastic transformation.
identifier
0ISSN: 0304-3835
1EISSN: 1872-7980
2DOI: 10.1016/j.canlet.2018.08.017
3PMID: 30144514
languageeng
publisherIreland: Elsevier B.V
subjectAdenocarcinoma ; Adenomatous polyposis coli ; Adenomatous Polyposis Coli Protein - genetics ; Adenomatous Polyposis Coli Protein - metabolism ; Analysis ; Apoptosis ; Apoptosis - genetics ; Article ; Barrett esophagus ; Barrett Esophagus - metabolism ; Barrett Esophagus - pathology ; Barrett's esophagus ; beta Catenin - genetics ; Cancer ; Cell activation ; Cell Differentiation - genetics ; Cell Movement - genetics ; Cell Proliferation - genetics ; Cell Transformation, Neoplastic - genetics ; Collagen ; Conflicts of interest ; CRISPR ; CRISPR-Cas Systems ; CRISPR/Cas9 ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Esophagus ; Gene Editing - methods ; Gene Knockout Techniques ; Genomes ; Genomics ; Humans ; Models ; Models, Genetic ; Mutation ; Neoplastic transformation ; Noise ; Organoids ; Organoids - metabolism ; Organoids - pathology ; Plasmids ; Signaling ; Transformation ; Tumor cell lines ; Tumorigenesis ; Wnt protein ; Wnt signaling ; Wnt Signaling Pathway - genetics ; β-Catenin
ispartofCancer letters, 2018-11-01, Vol.436, p.109-118
rights
02018 Elsevier B.V.
1Copyright © 2018 Elsevier B.V. All rights reserved.
2COPYRIGHT 2018 Elsevier B.V.
3Copyright Elsevier Limited Nov 1, 2018
lds50peer_reviewed
oafree_for_read
orcidid0000-0001-9535-1476
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
backlink$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30144514$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Liu, Xi
1Cheng, Yulan
2Abraham, John M
3Wang, Zhixiong
4Wang, Zhe
5Ke, Xiquan
6Yan, Rong
7Shin, Eun Ji
8Ngamruengphong, Saowanee
9Khashab, Mouen A
10Zhang, Guanjun
11McNamara, George
12Ewald, Andrew J
13Lin, DeChen
14Liu, Zhengwen
15Meltzer, Stephen J
title
0Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids
1Cancer letters
addtitleCancer Lett
descriptionPrimary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC-knockout (APCKO) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APCKO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise present in immortalized or cancer-derived cell lines. •A long-term expansion Wnt-activated human BE organoid model has been established using CRISPR-Cas9 combined with a niche-based selection system.•Compared to wild-type BE organoids, Wnt-activated BE organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, overexpression of Ki67, c-myc and cyclin D1, and enhanced protrusive migration ability, which disrupted reorganization and integrity of the basement membrane.•This CRISPR-Cas9 editing human-derived organoid model recapitulates the role of activated Wnt signaling during BE neoplastic transformation.
subject
0Adenocarcinoma
1Adenomatous polyposis coli
2Adenomatous Polyposis Coli Protein - genetics
3Adenomatous Polyposis Coli Protein - metabolism
4Analysis
5Apoptosis
6Apoptosis - genetics
7Article
8Barrett esophagus
9Barrett Esophagus - metabolism
10Barrett Esophagus - pathology
11Barrett's esophagus
12beta Catenin - genetics
13Cancer
14Cell activation
15Cell Differentiation - genetics
16Cell Movement - genetics
17Cell Proliferation - genetics
18Cell Transformation, Neoplastic - genetics
19Collagen
20Conflicts of interest
21CRISPR
22CRISPR-Cas Systems
23CRISPR/Cas9
24Deoxyribonucleic acid
25DNA
26DNA methylation
27Esophagus
28Gene Editing - methods
29Gene Knockout Techniques
30Genomes
31Genomics
32Humans
33Models
34Models, Genetic
35Mutation
36Neoplastic transformation
37Noise
38Organoids
39Organoids - metabolism
40Organoids - pathology
41Plasmids
42Signaling
43Transformation
44Tumor cell lines
45Tumorigenesis
46Wnt protein
47Wnt signaling
48Wnt Signaling Pathway - genetics
49β-Catenin
issn
00304-3835
11872-7980
fulltexttrue
rsrctypearticle
creationdate2018
recordtypearticle
recordideNp9kV9vFCEUxSdGY9fqNzCGxOdZYYY_My8mdVNtkxpN1fhILnBny2YWVmBN-u1lndpHw00IcM7hwq9pXjO6ZpTJd7u1hTBjWXeUDWtai6knzYoNqmvVONCnzYr2lLf90Iuz5kXOO0qp4Eo8b856yjgXjK-a9Dk6nH3Ykp-hkOy3Af6uzD3Z3F5_-3rbbiCPZIsh7pGg8-V0mtDCwZfjDAUzCRgPM2QPxAdyd9xDIB8gJSyFYFXd1XyYSUxbCNG7_LJ5NsGc8dXDfN78-Hj5fXPV3nz5dL25uGkt70VpJ6UkcuZ6K63sqMCOK9O5sVNG4iTrC81oxeisAj4a6ZTiwI0Uw-AGYybTnzdXS248YACfUB-S30O61xG8dgGLjk53UunBcsqYGkcQgg5oHAXWT46NwgFng6xRb5eoQ4q_jpiL3sVjql-Vdccol2PfCVFV60W1hRm1D1MsCWwdDvfexoCTr_sXQnCuKrS-GvhisCnmnHB67JBRfYKsd3qBrE-QNa3FVLW9eejmaPboHk3_qFbB-0WA9Xt_e0w6W4_BVnyVXNEu-v_f8Ae0Vbjj
startdate20181101
enddate20181101
creator
0Liu, Xi
1Cheng, Yulan
2Abraham, John M
3Wang, Zhixiong
4Wang, Zhe
5Ke, Xiquan
6Yan, Rong
7Shin, Eun Ji
8Ngamruengphong, Saowanee
9Khashab, Mouen A
10Zhang, Guanjun
11McNamara, George
12Ewald, Andrew J
13Lin, DeChen
14Liu, Zhengwen
15Meltzer, Stephen J
general
0Elsevier B.V
1Elsevier Limited
scope
0CGR
1CUY
2CVF
3ECM
4EIF
5NPM
6AAYXX
7CITATION
8BSHEE
93V.
107RV
117TO
127U9
137X7
147XB
1588E
1688G
178AO
188C1
198FE
208FH
218FI
228FJ
238FK
248G5
25ABUWG
26AZQEC
27BBNVY
28BENPR
29BHPHI
30DWQXO
31FYUFA
32GHDGH
33GNUQQ
34GUQSH
35H94
36HCIFZ
37K9.
38KB0
39LK8
40M0S
41M1P
42M2M
43M2O
44M7P
45MBDVC
46NAPCQ
47PADUT
48PQEST
49PQQKQ
50PQUKI
51PRINS
52Q9U
53BOBZL
54CLFQK
orcididhttps://orcid.org/0000-0001-9535-1476
sort
creationdate20181101
titleModeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids
authorLiu, Xi ; Cheng, Yulan ; Abraham, John M ; Wang, Zhixiong ; Wang, Zhe ; Ke, Xiquan ; Yan, Rong ; Shin, Eun Ji ; Ngamruengphong, Saowanee ; Khashab, Mouen A ; Zhang, Guanjun ; McNamara, George ; Ewald, Andrew J ; Lin, DeChen ; Liu, Zhengwen ; Meltzer, Stephen J
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-c435t-f776e41d3c6c6205e247b2d927b6ef6980b9c59dc7a49b6d774a4b6588d8bbfb3
rsrctypearticles
prefilterarticles
languageeng
creationdate2018
topic
0Adenocarcinoma
1Adenomatous polyposis coli
2Adenomatous Polyposis Coli Protein - genetics
3Adenomatous Polyposis Coli Protein - metabolism
4Analysis
5Apoptosis
6Apoptosis - genetics
7Article
8Barrett esophagus
9Barrett Esophagus - metabolism
10Barrett Esophagus - pathology
11Barrett's esophagus
12beta Catenin - genetics
13Cancer
14Cell activation
15Cell Differentiation - genetics
16Cell Movement - genetics
17Cell Proliferation - genetics
18Cell Transformation, Neoplastic - genetics
19Collagen
20Conflicts of interest
21CRISPR
22CRISPR-Cas Systems
23CRISPR/Cas9
24Deoxyribonucleic acid
25DNA
26DNA methylation
27Esophagus
28Gene Editing - methods
29Gene Knockout Techniques
30Genomes
31Genomics
32Humans
33Models
34Models, Genetic
35Mutation
36Neoplastic transformation
37Noise
38Organoids
39Organoids - metabolism
40Organoids - pathology
41Plasmids
42Signaling
43Transformation
44Tumor cell lines
45Tumorigenesis
46Wnt protein
47Wnt signaling
48Wnt Signaling Pathway - genetics
49β-Catenin
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Liu, Xi
1Cheng, Yulan
2Abraham, John M
3Wang, Zhixiong
4Wang, Zhe
5Ke, Xiquan
6Yan, Rong
7Shin, Eun Ji
8Ngamruengphong, Saowanee
9Khashab, Mouen A
10Zhang, Guanjun
11McNamara, George
12Ewald, Andrew J
13Lin, DeChen
14Liu, Zhengwen
15Meltzer, Stephen J
collection
0Medline
1MEDLINE
2MEDLINE (Ovid)
3MEDLINE
4MEDLINE
5PubMed
6CrossRef
7Academic OneFile (A&I only)
8ProQuest Central (Corporate)
9Nursing & Allied Health Database
10Oncogenes and Growth Factors Abstracts
11Virology and AIDS Abstracts
12Health & Medical Collection
13ProQuest Central (purchase pre-March 2016)
14Medical Database (Alumni Edition)
15Psychology Database (Alumni)
16ProQuest Pharma Collection
17Public Health Database
18ProQuest SciTech Collection
19ProQuest Natural Science Collection
20Hospital Premium Collection
21Hospital Premium Collection (Alumni Edition)
22ProQuest Central (Alumni) (purchase pre-March 2016)
23Research Library (Alumni Edition)
24ProQuest Central (Alumni Edition)
25ProQuest Central Essentials
26Biological Science Collection
27ProQuest Central
28Natural Science Collection
29ProQuest Central Korea
30Health Research Premium Collection
31Health Research Premium Collection (Alumni)
32ProQuest Central Student
33Research Library Prep
34AIDS and Cancer Research Abstracts
35SciTech Premium Collection
36ProQuest Health & Medical Complete (Alumni)
37Nursing & Allied Health Database (Alumni Edition)
38ProQuest Biological Science Collection
39Health & Medical Collection (Alumni Edition)
40Medical Database
41Psychology Database
42Research Library
43Biological Science Database
44Research Library (Corporate)
45Nursing & Allied Health Premium
46Research Library China
47ProQuest One Academic Eastern Edition
48ProQuest One Academic
49ProQuest One Academic UKI Edition
50ProQuest Central China
51ProQuest Central Basic
52OpenAIRE (Open Access)
53OpenAIRE
jtitleCancer letters
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Liu, Xi
1Cheng, Yulan
2Abraham, John M
3Wang, Zhixiong
4Wang, Zhe
5Ke, Xiquan
6Yan, Rong
7Shin, Eun Ji
8Ngamruengphong, Saowanee
9Khashab, Mouen A
10Zhang, Guanjun
11McNamara, George
12Ewald, Andrew J
13Lin, DeChen
14Liu, Zhengwen
15Meltzer, Stephen J
formatjournal
genrearticle
ristypeJOUR
atitleModeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids
jtitleCancer letters
addtitleCancer Lett
date2018-11-01
risdate2018
volume436
spage109
epage118
pages109-118
issn0304-3835
eissn1872-7980
abstractPrimary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC-knockout (APCKO) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APCKO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise present in immortalized or cancer-derived cell lines. •A long-term expansion Wnt-activated human BE organoid model has been established using CRISPR-Cas9 combined with a niche-based selection system.•Compared to wild-type BE organoids, Wnt-activated BE organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, overexpression of Ki67, c-myc and cyclin D1, and enhanced protrusive migration ability, which disrupted reorganization and integrity of the basement membrane.•This CRISPR-Cas9 editing human-derived organoid model recapitulates the role of activated Wnt signaling during BE neoplastic transformation.
copIreland
pubElsevier B.V
pmid30144514
doi10.1016/j.canlet.2018.08.017
orcididhttps://orcid.org/0000-0001-9535-1476
oafree_for_read