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dc.contributor.author
Fan, Z.
dc.contributor.author
Wirth, A.K.
dc.contributor.author
Chen, D.
dc.contributor.author
Wruck, C.J.
dc.contributor.author
Rauh, M.
dc.contributor.author
Buchfelder, Michael
dc.contributor.author
Savaskan, Nicolai
dc.date.accessioned
2018-01-26T15:44:52Z
dc.date.available
2017-12-12T05:40:39Z
dc.date.available
2018-01-26T15:44:52Z
dc.date.issued
2017
dc.identifier.issn
2157-9024
dc.identifier.other
10.1038/oncsis.2017.65
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/220101
dc.identifier.doi
10.3929/ethz-b-000220101
dc.description.abstract
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated. Nrf2 overexpression or Keap1 knockdown in glioma cells accelerate proliferation and oncogenic transformation. Further, activation of the Nrf2-Keap1 signaling upregulates xCT (aka SLC7A11 or system Xc−) and amplifies glutamate secretion thereby impacting on the tumor microenvironment. Moreover, both fostered Nrf2 expression and conversely Keap1 inhibition promote resistance to ferroptosis. Altogether, the Nrf2-Keap1 pathway operates as a switch for malignancy in gliomas promoting cell proliferation and resistance to cell death processes such as ferroptosis. Our data demonstrate that the Nrf2-Keap1 pathway is critical for cancer cell growth and operates on xCT. Nrf2 presents the Achilles’ heel of cancer cells and thus provides a valid therapeutic target for sensitizing cancer for chemotherapeutics.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-08-14
ethz.journal.title
Oncogenesis
ethz.journal.volume
6
en_US
ethz.pages.start
e371
en_US
ethz.size
14 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
New York, NY
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-12-12T05:40:41Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-01-26T15:45:02Z
ethz.rosetta.lastUpdated
2018-01-26T15:45:02Z
ethz.rosetta.versionExported
true
ethz.COinS
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