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dc.contributor.author
Xu, Pan
dc.contributor.author
Oosterveer, Maaike H.
dc.contributor.author
Stein, Sokrates
dc.contributor.author
Demagny, Hadrien
dc.contributor.author
Ryu, Dongryeol
dc.contributor.author
Moullan, Norman
dc.contributor.author
Wang, Xu
dc.contributor.author
Can, Emine
dc.contributor.author
Zamboni, Nicola
dc.contributor.author
Comment, Arnaud
dc.contributor.author
Auwerx, Johan
dc.contributor.author
Schoonjans, Kristina
dc.date.accessioned
2023-09-12T10:28:40Z
dc.date.available
2017-06-12T08:07:07Z
dc.date.available
2023-09-12T10:28:40Z
dc.date.issued
2016
dc.identifier.issn
0890-9369
dc.identifier.issn
1549-5477
dc.identifier.other
10.1101/gad.277483.116
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/117742
dc.identifier.doi
10.3929/ethz-b-000117742
dc.description.abstract
Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncanonical glutamine pathway that is reliant on the mitochondrial and cytosolic transaminases glutamate pyruvate transaminase 2 (GPT2) and glutamate oxaloacetate transaminase 1 (GOT1), which fuel anabolic metabolism. In particular, we show that gain and loss of function of hepatic LRH-1 modulate the expression and activity of mitochondrial glutaminase 2 (GLS2), the first and rate-limiting step of this pathway. Acute and chronic deletion of hepatic LRH-1 blunts the deamination of glutamine and reduces glutamine-dependent anaplerosis. The robust reduction in glutaminolysis and the limiting availability of α-ketoglutarate in turn inhibit mTORC1 signaling to eventually block cell growth and proliferation. Collectively, these studies highlight the importance of LRH-1 in coordinating glutamine-induced metabolism and signaling to promote hepatocellular carcinogenesis.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Cold Spring Harbor Laboratory Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.subject
Hepatocellular carcinoma
en_US
dc.subject
Cancer metabolism
en_US
dc.subject
Nuclear receptor NR5A2
en_US
dc.subject
Mitochondria
en_US
dc.subject
Anaplerosis
en_US
dc.subject
mTOR
en_US
dc.subject
NADPH
en_US
dc.title
LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 4.0 International
dc.date.published
2016
ethz.journal.title
Genes & Development
ethz.journal.volume
30
en_US
ethz.journal.issue
11
en_US
ethz.journal.abbreviated
Genes & Dev
ethz.pages.start
1255
en_US
ethz.pages.end
1260
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
000038328
ethz.publication.place
Cold Spring Harbor, NY
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03713 - Sauer, Uwe / Sauer, Uwe
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03713 - Sauer, Uwe / Sauer, Uwe
ethz.date.deposited
2017-06-12T08:11:52Z
ethz.source
ECIT
ethz.identifier.importid
imp5936547f33c8456033
ethz.ecitpid
pub:179659
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T11:30:37Z
ethz.rosetta.lastUpdated
2024-02-03T03:26:43Z
ethz.rosetta.versionExported
true
ethz.COinS
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