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dc.contributor.author
Guccini, Ilaria
dc.contributor.author
Tang, Guanghui
dc.contributor.author
To, Trang T.
dc.contributor.author
Di Rito, Laura
dc.contributor.author
Le Blanc, Solange
dc.contributor.author
Strobel, Oliver
dc.contributor.author
D'Ambrosio, Mariantonietta
dc.contributor.author
Pasquini, Emiliano
dc.contributor.author
Bolis, Marco
dc.contributor.author
Silva, Pamuditha
dc.contributor.author
Kabakci, Hasan A.
dc.contributor.author
Godbersen, Svenja
dc.contributor.author
Alimonti, Andrea
dc.contributor.author
Schwank, Gerald
dc.contributor.author
Stoffel, Markus
dc.date.accessioned
2024-02-02T11:03:32Z
dc.date.available
2024-02-02T11:03:32Z
dc.date.issued
2023-08-18
dc.identifier.issn
2589-0042
dc.identifier.other
10.1016/j.isci.2023.107368
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/657270
dc.identifier.doi
10.3929/ethz-b-000625922
dc.description.abstract
Although dietary fructose is associated with an elevated risk for pancreatic cancer, the underlying mechanisms remain elusive. Here, we report that ketohexokinase (KHK), the rate-limiting enzyme of fructose metabolism, is a driver of PDAC development. We demonstrate that fructose triggers KHK and induces fructolytic gene expression in mouse and human PDAC. Genetic inactivation of KhkC enhances the survival of KPC-driven PDAC even in the absence of high fructose diet. Furthermore, it decreases the viability, migratory capability, and growth of KPC cells in a cell autonomous manner. Mechanistically, we demonstrate that genetic ablation of KHKC strongly impairs the activation of KRAS-MAPK pathway and of rpS6, a downstream target of mTORC signaling. Moreover, overexpression of KHKC in KPC cells enhances the downstream KRAS pathway and cell viability. Our data provide new insights into the role of KHK in PDAC progression and imply that inhibiting KHK could have profound implications for pancreatic cancer therapy.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Natural sciences
en_US
dc.subject
Biological sciences
en_US
dc.subject
Biochemistry
en_US
dc.subject
Systems biology
en_US
dc.subject
Cancer systems biology
en_US
dc.title
Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2023-07-13
ethz.journal.title
iScience
ethz.journal.volume
26
en_US
ethz.journal.issue
8
en_US
ethz.pages.start
107368
en_US
ethz.size
30 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Roles of ketohexokinase signaling and fructose metabolism in pancreatic tumor growth
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Amsterdam
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09703 - Alimonti, Andrea / Alimonti, Andrea
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03739 - Stoffel, Markus / Stoffel, Markus
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09703 - Alimonti, Andrea / Alimonti, Andrea
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03739 - Stoffel, Markus / Stoffel, Markus
ethz.grant.agreementno
176317
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projekte Lebenswissenschaften
ethz.date.deposited
2023-08-08T07:18:05Z
ethz.source
BATCH
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2024-02-02T11:03:37Z
ethz.rosetta.lastUpdated
2024-02-02T11:03:37Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/656955
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/625922
ethz.COinS
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