TY  - JOUR
AU  - Triki, Mouna
AU  - Rinaldi, Gianmarco
AU  - Planque, Melanie
AU  - Broekaert, Dorien
AU  - Winkelkotte, Alina M
AU  - Maier, Carina R
AU  - Janaki Raman, Sudha
AU  - Vandekeere, Anke
AU  - Van Elsen, Joke
AU  - Orth, Martin F
AU  - Grünewald, Thomas G P
AU  - Schulze, Almut
AU  - Fendt, Sarah-Maria
TI  - mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis.
JO  - Cell reports
VL  - 31
IS  - 12
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2020-01122
SP  - 107806
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32579932
DO  - DOI:10.1016/j.celrep.2020.107806
UR  - https://inrepo02.dkfz.de/record/156805
ER  -