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mTOR signaling and SREBP activity increase FADS2 expression and can activate sapienate biosynthesis

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-b...

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Main Authors: Triki, Mouna (Author) , Rinaldi, Gianmarco (Author) , Planque, Melanie (Author) , Broekaert, Dorien (Author) , Winkelkotte, Alina M. (Author) , Maier, Carina R. (Author) , Janaki Raman, Sudha (Author) , Vandekeere, Anke (Author) , Van Elsen, Joke (Author) , Orth, Martin F. (Author) , Grünewald, Thomas G. P. (Author) , Schulze, Almut (Author) , Fendt, Sarah-Maria (Author)
Format: Article (Journal)
Language:English
Published: June 23, 2020
In: Cell reports
Year: 2020, Volume: 31, Issue: 12
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.107806
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2020.107806
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Author Notes:Mouna Triki, Gianmarco Rinaldi, Melanie Planque, Dorien Broekaert, Alina M. Winkelkotte, Carina R. Maier, Sudha Janaki Raman, Anke Vandekeere, Joke Van Elsen, Martin F. Orth, Thomas G.P. Grünewald, Almut Schulze, and Sarah-Maria Fendt
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Summary: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.
Item Description:Gesehen am 18.08.2020
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.107806

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