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dc.contributor.author
Christen, Stefan
dc.contributor.author
Lorendeau, Doriane
dc.contributor.author
Schmieder, Roberta
dc.contributor.author
Broekaert, Dorien
dc.contributor.author
Metzger, Kristine
dc.contributor.author
Veys, Koen
dc.contributor.author
Elia, Ilaria
dc.contributor.author
Buescher, Joerg M.
dc.contributor.author
Orth, Martin F.
dc.contributor.author
Davidson, Shawn M.
dc.contributor.author
Grünewald, Thomas G.P.
dc.contributor.author
De Bock, Katrien
dc.contributor.author
Fendt, Sarah-Maria
dc.date.accessioned
2018-09-17T08:17:06Z
dc.date.available
2017-06-12T14:30:14Z
dc.date.available
2018-09-17T08:17:06Z
dc.date.issued
2016-10
dc.identifier.other
10.1016/j.celrep.2016.09.042
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/121670
dc.identifier.doi
10.3929/ethz-b-000121670
dc.description.abstract
Cellular proliferation depends on refilling the tricarboxylic acid (TCA) cycle to support biomass production (anaplerosis). The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC) and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo 13C tracer analysis. We discovered that lung metastases have higher PC-dependent anaplerosis compared to primary breast cancers. Based on in vitro analysis and a mathematical model for the determination of compartment-specific metabolite concentrations, we found that mitochondrial pyruvate concentrations can promote PC-dependent anaplerosis via enzyme kinetics. In conclusion, we show that breast cancer cells proliferating as lung metastases activate PC-dependent anaplerosis in response to the lung microenvironment.
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-nc-nd/4.0/
dc.subject
pyruvate carboxylase
en_US
dc.subject
mitochondrial pyruvate concentration
en_US
dc.subject
lung metastasis
en_US
dc.subject
breast cancer
en_US
dc.subject
TCA cycle anaplerosis
en_US
dc.subject
microenvironment
en_US
dc.subject
glycolytic metabolism
en_US
dc.subject
cancer metabolism
en_US
dc.subject
13C tracer analysis
en_US
dc.subject
pyruvate metabolism
en_US
dc.title
Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2016-10-11
ethz.journal.title
Cell Reports
ethz.journal.volume
17
en_US
ethz.journal.issue
3
en_US
ethz.pages.start
837
en_US
ethz.pages.end
848
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
007612702
ethz.publication.place
New York, NY
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::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09560 - De Bock, Katrien / De Bock, Katrien
en_US
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::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09560 - De Bock, Katrien / De Bock, Katrien
ethz.date.deposited
2017-06-12T14:36:16Z
ethz.source
ECIT
ethz.identifier.importid
imp593654cb3ba7a12175
ethz.ecitpid
pub:183787
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T00:01:39Z
ethz.rosetta.lastUpdated
2018-11-08T02:20:13Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Breast%20Cancer-Derived%20Lung%20Metastases%20Show%20Increased%20Pyruvate%20Carboxylase-Dependent%20Anaplerosis&rft.jtitle=Cell%20Reports&rft.date=2016-10&rft.volume=17&rft.issue=3&rft.spage=837&rft.epage=848&rft.au=Christen,%20Stefan&Lorendeau,%20Doriane&Schmieder,%20Roberta&Broekaert,%20Dorien&Metzger,%20Kristine&rft.genre=article&
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