Cholesterol Pathway Inhibition Induces TGF-β Signaling to Promote Basal Differentiation in Pancreatic Cancer.
3-Hydroxysteroid Dehydrogenases
/ genetics
Animals
Atorvastatin
/ pharmacology
Biosynthetic Pathways
/ genetics
Carcinoma, Pancreatic Ductal
/ drug therapy
Cell Differentiation
/ drug effects
Cell Line, Tumor
Cholesterol, LDL
/ biosynthesis
Epithelial-Mesenchymal Transition
/ drug effects
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ pharmacology
Kaplan-Meier Estimate
Mice, Inbred C57BL
Mice, Knockout
Pancreatic Neoplasms
/ drug therapy
Signal Transduction
/ genetics
Transforming Growth Factor beta
/ genetics
Xenograft Model Antitumor Assays
/ methods
TGF-β signaling
cholesterol metabolism
epithelial-to-mesenchymal transition
pancreatic cancer
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
12 10 2020
12 10 2020
Historique:
received:
30
04
2019
revised:
11
06
2020
accepted:
21
08
2020
pubmed:
26
9
2020
medline:
9
3
2021
entrez:
25
9
2020
Statut:
ppublish
Résumé
Oncogenic transformation alters lipid metabolism to sustain tumor growth. We define a mechanism by which cholesterol metabolism controls the development and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of the rate-limiting enzyme Nsdhl or treatment with cholesterol-lowering statins switches glandular pancreatic carcinomas to a basal (mesenchymal) phenotype in mouse models driven by Kras
Identifiants
pubmed: 32976774
pii: S1535-6108(20)30426-8
doi: 10.1016/j.ccell.2020.08.015
pmc: PMC7572882
mid: NIHMS1631266
pii:
doi:
Substances chimiques
Cholesterol, LDL
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Transforming Growth Factor beta
0
Atorvastatin
A0JWA85V8F
3-Hydroxysteroid Dehydrogenases
EC 1.1.-
Nsdhl protein, mouse
EC 1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
567-583.e11Subventions
Organisme : NCI NIH HHS
ID : R21 CA164205
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA231252
Pays : United States
Organisme : NIH HHS
ID : S10 OD023666
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA188430
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA221838
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA160725
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA232256
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108195
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD065800
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006927
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009035
Pays : United States
Organisme : NIH HHS
ID : S10 OD023586
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA113451
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests I.A. served as a consultant for Caris Life Sciences, Inc.
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