HNF1A recruits KDM6A to activate differentiated acinar cell programs that suppress pancreatic cancer.
Acinar Cells
/ metabolism
Animals
Carcinoma, Pancreatic Ductal
/ genetics
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Hepatocyte Nuclear Factor 1-alpha
/ genetics
Histone Demethylases
/ genetics
Humans
Mice
Mutation
Organ Specificity
Pancreas
/ metabolism
Pancreatic Neoplasms
/ genetics
HNF1A
KDM6A
non-classical PDAC
pancreas
pancreas differentiation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
01
07
2019
revised:
02
02
2020
accepted:
07
02
2020
pubmed:
11
3
2020
medline:
15
12
2020
entrez:
11
3
2020
Statut:
ppublish
Résumé
Defects in transcriptional regulators of pancreatic exocrine differentiation have been implicated in pancreatic tumorigenesis, but the molecular mechanisms are poorly understood. The locus encoding the transcription factor HNF1A harbors susceptibility variants for pancreatic ductal adenocarcinoma (PDAC), while KDM6A, encoding Lysine-specific demethylase 6A, carries somatic mutations in PDAC. Here, we show that pancreas-specific Hnf1a null mutant transcriptomes phenocopy those of Kdm6a mutations, and both defects synergize with Kras
Identifiants
pubmed: 32154941
doi: 10.15252/embj.2019102808
pmc: PMC7196917
doi:
Substances chimiques
HNF1A protein, human
0
Hepatocyte Nuclear Factor 1-alpha
0
Histone Demethylases
EC 1.14.11.-
KDM6A protein, human
EC 1.14.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e102808Subventions
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : RTI2018-095666-B-I00
Pays : International
Organisme : MEC|Instituto de Salud Carlos III (ISCIII)
ID : RD12/0036/0034
Pays : International
Organisme : Wellcome Trust (WT)
ID : WT101033
Pays : International
Organisme : Generalitat de Catalunya (Government of Catalonia)
Pays : International
Organisme : Medical Research Council
ID : MR/L02036X/1
Pays : United Kingdom
Organisme : MEC|Instituto de Salud Carlos III (ISCIII)
ID : RD12/0036/0050
Pays : International
Organisme : European Research Council Advanced Grant
ID : 789055
Pays : International
Organisme : NICHD NIH HHS
ID : R01 HD024462
Pays : United States
Organisme : CERCA Programme
Pays : International
Organisme : UK Research and Innovation|Medical Research Council (MRC)
ID : MR/L02036X/1
Pays : International
Organisme : Ministerio de Ciencia, Innovación y Universidades Ministry of Science, Innovation and Universities
ID : SEV-2016-0510
Pays : International
Organisme : Juvenile Diabetes Research Foundation United States of America (JDRF)
ID : 3-PDF-2014-192-A-N
Pays : International
Organisme : Fundación Bancaja (Fundació Bancaixa)
ID : LCF/BQ/ES18/11670009
Pays : International
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : SAF2015-70553-R
Pays : International
Organisme : Ministerio de Ciencia, Innovación y Universidades Ministry of Science, Innovation and Universities
ID : SEV-2012-0208
Pays : International
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : BFU2014-54284-R
Pays : International
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : SAF2011-29530
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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