PMID- 32579932
OWN - NLM
STAT- MEDLINE
DCOM- 20210428
LR  - 20211204
IS  - 2211-1247 (Electronic)
VI  - 31
IP  - 12
DP  - 2020 Jun 23
TI  - mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate 
      Sapienate Biosynthesis.
PG  - 107806
LID - S2211-1247(20)30787-7 [pii]
LID - 10.1016/j.celrep.2020.107806 [doi]
LID - 107806
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.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Triki, Mouna
AU  - Triki M
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
FAU - Rinaldi, Gianmarco
AU  - Rinaldi G
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
FAU - Planque, Melanie
AU  - Planque M
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
FAU - Broekaert, Dorien
AU  - Broekaert D
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
FAU - Winkelkotte, Alina M
AU  - Winkelkotte AM
AD  - Division of Tumor Metabolism and Microenvironment, German Cancer Research Center, 
      Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; Faculty of Biosciences, 
      University of Heidelberg, 69120 Heidelberg, Germany.
FAU - Maier, Carina R
AU  - Maier CR
AD  - Biochemistry and Molecular Biology, Theodor-Boveri-Institute, Biocenter, Am 
      Hubland, 97074 Wurzburg, Germany.
FAU - Janaki Raman, Sudha
AU  - Janaki Raman S
AD  - Biochemistry and Molecular Biology, Theodor-Boveri-Institute, Biocenter, Am 
      Hubland, 97074 Wurzburg, Germany.
FAU - Vandekeere, Anke
AU  - Vandekeere A
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
FAU - Van Elsen, Joke
AU  - Van Elsen J
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
FAU - Orth, Martin F
AU  - Orth MF
AD  - Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, 
      Faculty of Medicine, LMU Munich, Thalkirchner Strasse 36, 80337 Munich, Germany.
FAU - Grunewald, Thomas G P
AU  - Grunewald TGP
AD  - Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, 
      Faculty of Medicine, LMU Munich, Thalkirchner Strasse 36, 80337 Munich, Germany; 
      German Cancer Consortium (DKTK), partner site Munich, 80337 Munich, Germany; 
      Division of Translational Pediatric Sarcoma Research, German Cancer Research 
      Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Institute of 
      Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 
      Heidelberg, Germany.
FAU - Schulze, Almut
AU  - Schulze A
AD  - Division of Tumor Metabolism and Microenvironment, German Cancer Research Center, 
      Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; Biochemistry and Molecular 
      Biology, Theodor-Boveri-Institute, Biocenter, Am Hubland, 97074 Wurzburg, 
      Germany.
FAU - Fendt, Sarah-Maria
AU  - Fendt SM
AD  - Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center 
      for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of 
      Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven 
      and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium. 
      Electronic address: sarah-maria.fendt@kuleuven.vib.be.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Palmitic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (delta(6)-hexadecenoic acid)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.19.3 (FADS2 protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Fatty Acid Desaturases/*genetics/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Palmitic Acids/*metabolism
MH  - Prognosis
MH  - RNA, Messenger/genetics/metabolism
MH  - *Signal Transduction
MH  - Sterol Regulatory Element Binding Protein 1/*biosynthesis/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcription, Genetic
PMC - PMC7326293
OTO - NOTNLM
OT  - FADS2
OT  - SCD1
OT  - SREBP
OT  - cancer
OT  - fatty acid metabolism
OT  - glioblastoma
OT  - hepatocellular carcinoma
OT  - mTOR
OT  - palmitate
OT  - palmitoleate
OT  - sapienate
COIS- Declaration of Interests S.-M.F. has received funding from Bayer, Merck, and 
      Black Belt Therapeutics and has consulted for Funds+.
EDAT- 2020/06/25 06:00
MHDA- 2021/04/29 06:00
PMCR- 2020/06/23
CRDT- 2020/06/25 06:00
PHST- 2019/10/28 00:00 [received]
PHST- 2020/04/03 00:00 [revised]
PHST- 2020/06/02 00:00 [accepted]
PHST- 2020/06/25 06:00 [entrez]
PHST- 2020/06/25 06:00 [pubmed]
PHST- 2021/04/29 06:00 [medline]
PHST- 2020/06/23 00:00 [pmc-release]
AID - S2211-1247(20)30787-7 [pii]
AID - 107806 [pii]
AID - 10.1016/j.celrep.2020.107806 [doi]
PST - ppublish
SO  - Cell Rep. 2020 Jun 23;31(12):107806. doi: 10.1016/j.celrep.2020.107806.