Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8645
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dc.contributor.authorMooz, Juliane-
dc.contributor.authorRiegel, Kristina-
dc.contributor.authorPs, Hari-
dc.contributor.authorSadanandam, Anguraj-
dc.contributor.authorMarini, Federico-
dc.contributor.authorKlein, Matthias-
dc.contributor.authorWerner, Ulrike-
dc.contributor.authorRoth, Wilfried-
dc.contributor.authorWilken-Schmitz, Annett-
dc.contributor.authorTegeder, Irmgard-
dc.contributor.authorRajalingam, Krishnaraj-
dc.date.accessioned2023-01-25T12:02:32Z-
dc.date.available2023-01-25T12:02:32Z-
dc.date.issued2022-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8661-
dc.description.abstractRAF kinases are highly conserved serine/threonine kinases, and among the three RAF isoforms (ARAF, BRAF, and CRAF), the pathophysiological relevance of ARAF is not well defined. Here, we show that patients with lung cancer exhibit low expression of ARAF, which is associated with lymph node metastasis and poor patient survival. We uncover that depletion of ARAF promotes anchorage-independent growth and metastasis through activation of AKT signaling in a subset of lung cancer cells. We identified that loss of ARAF was associated with an increase in ERBB3 expression in a kinase-independent manner. ARAF suppressed the promoter activity of ERBB3, and reconstitution of ARAF in ARAF-depleted cells led to the reversal of enhanced ERBB3-AKT signaling. Furthermore, ARAF inhibited neuregulin 1 (hNRG1)–mediated AKT activation through controlling ERBB3 expression via the transcription factor KLF5. Our results disclose a critical dual role for ARAF kinase in the negative regulation of ERBB3-AKT signaling, thereby suppressing tumor metastasis.en_GB
dc.description.sponsorshipGefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577de
dc.language.isoengde
dc.rightsCC BY-NC*
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleARAF suppresses ERBB3 expression and metastasis in a subset of lung cancersen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-8645-
jgu.type.contenttypeScientific articlede
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleScience advancesde
jgu.journal.volume8de
jgu.journal.issue11de
jgu.pages.alternativeeabk1538de
jgu.publisher.year2022-
jgu.publisher.nameAssoc.de
jgu.publisher.placeWashington, DC u.a.de
jgu.publisher.issn2375-2548de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1126/sciadv.abk1538de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgLebenswissenschaftende
Appears in collections:DFG-491381577-G

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