The complexities and versatility of the RAS-to-ERK signalling system in normal and cancer cells

DC FieldValueLanguage
dc.contributor.authorFey, Dirk-
dc.contributor.authorMatallanas, David-
dc.contributor.authorRauch, Jens-
dc.contributor.authorRukhlenko, Oleksii S.-
dc.contributor.authorKholodenko, Boris N.-
dc.date.accessioned2019-04-02T11:12:23Z-
dc.date.available2019-04-02T11:12:23Z-
dc.date.copyright2016 Elsevieren_US
dc.date.issued2016-10-
dc.identifier.citationSeminars in Cell & Developmental Biologyen_US
dc.identifier.urihttp://hdl.handle.net/10197/9769-
dc.description.abstractThe intricate dynamic control and plasticity of RAS to ERK mitogenic, survival and apoptotic signalling has mystified researches for more than 30 years. Therapeutics targeting the oncogenic aberrations within this pathway often yield unsatisfactory, even undesired results, as in the case of paradoxical ERK activation in response to RAF inhibition. A direct approach of inhibiting single oncogenic proteins misses the dynamic network context governing the network signal processing. In this review, we discuss the signalling behaviour of RAS and RAF proteins in normal and in cancer cells, and the emerging systems-level properties of the RAS-to-ERK signalling network. We argue that to understand the dynamic complexities of this control system, mathematical models including mechanistic detail are required. Looking into the future, these dynamic models will build the foundation upon which more effective, rational approaches to cancer therapy will be developed.en_US
dc.description.sponsorshipEuropean Commission Horizon 2020en_US
dc.description.sponsorshipEuropean Commission - Seventh Framework Programme (FP7)en_US
dc.description.sponsorshipScience Foundation Irelanden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsThis is the author’s version of a work that was accepted for publication in Seminars in Cell & Developmental Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Seminars in Cell & Developmental Biology (58, (2016)) https://doi.org/10.1016/j.semcdb.2016.06.011en_US
dc.subjectDynamic modellingen_US
dc.subjectMAPK cascadeen_US
dc.subjectSystems biologyen_US
dc.titleThe complexities and versatility of the RAS-to-ERK signalling system in normal and cancer cellsen_US
dc.typeReviewen_US
dc.statusPeer revieweden_US
dc.identifier.volume58en_US
dc.identifier.startpage96en_US
dc.identifier.endpage107en_US
dc.identifier.doi10.1016/j.semcdb.2016.06.011-
dc.neeo.contributorFey|Dirk|aut|-
dc.neeo.contributorMatallanas|David|aut|-
dc.neeo.contributorRauch|Jens|aut|-
dc.neeo.contributorRukhlenko|Oleksii S.|aut|-
dc.neeo.contributorKholodenko|Boris N.|aut|-
dc.date.updated2017-12-06-
dc.identifier.grantid613879-
dc.identifier.grantid14/IA/2395-
dc.identifier.grantid686098-
item.fulltextWith Fulltext-
item.grantfulltextopen-
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