mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis.
Animals
Cell Line, Tumor
Fatty Acid Desaturases
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Mice
Palmitic Acids
/ metabolism
Prognosis
RNA, Messenger
/ genetics
Signal Transduction
Sterol Regulatory Element Binding Protein 1
/ biosynthesis
TOR Serine-Threonine Kinases
/ metabolism
Transcription, Genetic
FADS2
SCD1
SREBP
cancer
fatty acid metabolism
glioblastoma
hepatocellular carcinoma
mTOR
palmitate
palmitoleate
sapienate
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
23 06 2020
23 06 2020
Historique:
received:
28
10
2019
revised:
03
04
2020
accepted:
02
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
29
4
2021
Statut:
ppublish
Résumé
Cancer cells display an increased plasticity in their lipid metabolism, which includes the conversion of palmitate to sapienate via the enzyme fatty acid desaturase 2 (FADS2). We find that FADS2 expression correlates with mammalian target of rapamycin (mTOR) signaling and sterol regulatory element-binding protein 1 (SREBP-1) activity across multiple cancer types and is prognostic in some cancer types. Accordingly, activating mTOR signaling by deleting tuberous sclerosis complex 2 (Tsc2) or overexpression of SREBP-1/2 is sufficient to increase FADS2 mRNA expression and sapienate metabolism in mouse embryonic fibroblasts (MEFs) and U87 glioblastoma cells, respectively. Conversely, inhibiting mTOR signaling decreases FADS2 expression and sapienate biosynthesis in MEFs with Tsc2 deletion, HUH7 hepatocellular carcinoma cells, and orthotopic HUH7 liver xenografts. In conclusion, we show that mTOR signaling and SREBP activity are sufficient to activate sapienate metabolism by increasing FADS2 expression. Consequently, targeting mTOR signaling can reduce sapienate metabolism in vivo.
Identifiants
pubmed: 32579932
pii: S2211-1247(20)30787-7
doi: 10.1016/j.celrep.2020.107806
pmc: PMC7326293
pii:
doi:
Substances chimiques
Palmitic Acids
0
RNA, Messenger
0
Sterol Regulatory Element Binding Protein 1
0
delta(6)-hexadecenoic acid
0
Fatty Acid Desaturases
EC 1.14.19.-
FADS2 protein, human
EC 1.14.19.3
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107806Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests S.-M.F. has received funding from Bayer, Merck, and Black Belt Therapeutics and has consulted for Funds+.