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dc.contributor.authorCastellano, E
dc.contributor.authorMolina-Arcas, M
dc.contributor.authorKrygowska, AA
dc.contributor.authorEast, P
dc.contributor.authorWarne, P
dc.contributor.authorNicol, A
dc.contributor.authorDownward, J
dc.date.accessioned2020-06-22T15:47:59Z
dc.date.issued2016-04-13
dc.identifier.citationNature communications, 2016, 7 pp. 11245 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3771
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms11245
dc.description.abstractRAS signalling through phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumour invasiveness, but the role of direct RAS binding to PI3-Kinase in this remains uncertain. Here, we provide evidence that disruption of RAS interaction with PI3-Kinase p110α decreases cell motility and prevents activation of Rac GTPase. Analysis of gene expression in cells lacking RAS interaction with p110α reveals increased levels of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resulting in upregulation of E-cadherin expression. Induction of the Reelin/E-cadherin axis is also observed in Kras mutant lung tumours that are regressing due to blockade of RAS interaction with PI3-Kinase. Furthermore, loss of Reelin correlates with decreased survival of lung and breast cancer patients. Reelin thus plays a role in restraining RAS and PI3-kinase promotion of cell motility and potentially tumour metastasis.
dc.formatElectronic
dc.format.extent11245 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectMice
dc.subjectLung Neoplasms
dc.subjectras Proteins
dc.subjectrac1 GTP-Binding Protein
dc.subjectSerine Endopeptidases
dc.subjectCadherins
dc.subjectCell Adhesion Molecules, Neuronal
dc.subjectNerve Tissue Proteins
dc.subjectExtracellular Matrix Proteins
dc.subjectSignal Transduction
dc.subjectCell Movement
dc.subjectCell Polarity
dc.subjectUp-Regulation
dc.subjectEnzyme Activation
dc.subjectProtein Binding
dc.subjectPhosphatidylinositol 3-Kinases
dc.titleRAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.
dc.typeJournal Article
dcterms.dateAccepted2016-03-03
rioxxterms.versionofrecord10.1038/ncomms11245
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-04-13
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.publication-statusPublished
pubs.volume7en_US
pubs.embargo.termsNot known
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorDownward, Julian David Harryen


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