Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans.
Animals
Biosynthetic Pathways
/ drug effects
Carcinogenesis
/ genetics
Carcinoma, Hepatocellular
/ genetics
Cell Line, Tumor
Cholesterol
/ biosynthesis
Fatty Acid Synthase, Type I
/ genetics
Fatty Acids
/ biosynthesis
Female
Gene Knockdown Techniques
Gene Silencing
Genomics
Humans
Hydroxymethylglutaryl CoA Reductases
/ genetics
Lipidomics
Liver Neoplasms
/ genetics
Male
Mice
Mice, Knockout
PTEN Phosphohydrolase
/ metabolism
Proto-Oncogene Proteins c-met
/ metabolism
Sterol Regulatory Element Binding Protein 2
/ genetics
Transcriptome
Cholesterol biosynthesis
Fatty acid synthase
HMG-CoA reductase
Hepatocellular carcinoma
Systems biology
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
12
09
2018
revised:
14
03
2019
accepted:
15
03
2019
pubmed:
8
4
2019
medline:
24
12
2019
entrez:
8
4
2019
Statut:
ppublish
Résumé
Increased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC). We investigated the functional contribution of fatty acid synthase (Fasn)-mediated de novo FA synthesis in a murine HCC model induced by loss of Pten and overexpression of c-Met (sgPten/c-Met) using liver-specific Ablation of Our study uncovers a novel functional crosstalk between aberrant lipogenesis and cholesterol biosynthesis pathways in hepatocarcinogenesis, whose concomitant inhibition might represent a therapeutic option for HCC.
Identifiants
pubmed: 30954949
pii: gutjnl-2018-317581
doi: 10.1136/gutjnl-2018-317581
pmc: PMC6943247
doi:
Substances chimiques
Fatty Acids
0
SREBF2 protein, human
0
Srebf2 protein, mouse
0
Sterol Regulatory Element Binding Protein 2
0
Cholesterol
97C5T2UQ7J
HMGCR protein, human
EC 1.1.1.-
Hydroxymethylglutaryl CoA Reductases
EC 1.1.1.-
FASN protein, human
EC 2.3.1.85
Fasn protein, mouse
EC 2.3.1.85
Fatty Acid Synthase, Type I
EC 2.3.1.85
Proto-Oncogene Proteins c-met
EC 2.7.10.1
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
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
Pagination
177-186Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK026743
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136606
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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