FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion

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dc.contributor.author Stanicka, Joanna
dc.contributor.author Rieger, Leonie
dc.contributor.author O'Shea, Sandra
dc.contributor.author Cox, Orla T.
dc.contributor.author Coleman, Michael
dc.contributor.author O'Flanagan, Ciara
dc.contributor.author Addario, Barbara
dc.contributor.author McCabe, Nuala
dc.contributor.author Kennedy, Richard
dc.contributor.author O'Connor, Rosemary
dc.date.accessioned 2018-11-09T12:00:40Z
dc.date.available 2018-11-09T12:00:40Z
dc.date.issued 2018-03-15
dc.identifier.citation Stanicka, J., Rieger, L., O’Shea, S., Cox, O., Coleman, M., O’Flanagan, C., Addario, B., McCabe, N., Kennedy, R. and O’Connor, R. (2018) 'FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion', Oncogene, 37(23), pp. 3131-3150. doi: 10.1038/s41388-017-0113-z en
dc.identifier.volume 37 en
dc.identifier.startpage 3131 en
dc.identifier.endpage 3150 en
dc.identifier.issn 0950-9232
dc.identifier.uri http://hdl.handle.net/10468/7082
dc.identifier.doi 10.1038/s41388-017-0113-z
dc.description.abstract IGF-1 receptor (IGF-1R) and integrin cooperative signaling promotes cancer cell survival, proliferation, and motility, but whether this influences cancer progression and therapy responses is largely unknown. Here we investigated the non-receptor tyrosine adhesion kinase FES-related (FER), following its identification as a potential mediator of sensitivity to IGF-1R kinase inhibition in a functional siRNA screen. We found that FER and the IGF-1R co-locate in cells and can be co-immunoprecipitated. Ectopic FER expression strongly enhanced IGF-1R expression and phosphorylation on tyrosines 950 and 1131. FER phosphorylated these sites in an IGF-1R kinase-independent manner and also enhanced IGF-1-mediated phosphorylation of SHC, and activation of either AKT or MAPK-signaling pathways in different cells. The IGF-1R, β1 Integrin, FER, and its substrate cortactin were all observed to co-locate in cell adhesion complexes, the disruption of which reduced IGF-1R expression and activity. High FER expression correlates with phosphorylation of SHC in breast cancer cell lines and with a poor prognosis in patient cohorts. FER and SHC phosphorylation and IGF-1R expression could be suppressed with a known anaplastic lymphoma kinase inhibitor (AP26113) that shows high specificity for FER kinase. Overall, we conclude that FER enhances IGF-1R expression, phosphorylation, and signaling to promote cooperative growth and adhesion signaling that may facilitate cancer progression. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Springer Nature en
dc.relation.uri https://www.nature.com/articles/s41388-017-0113-z
dc.rights © Macmillan Publishers Limited, part of Springer Nature 2018 en
dc.subject Breast cancer en
dc.subject Cortactin phosphorylation en
dc.subject Carcinoma cells en
dc.subject IGF-1 receptor en
dc.subject Resistance en
dc.subject Protein en
dc.subject SRC en
dc.subject Metastasis en
dc.subject Expression en
dc.subject Migration en
dc.title FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Rosemary O'Connor, School Of Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: r.oconnor@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-11-09T08:42:14Z
dc.description.version Accepted Version en
dc.internal.rssid 442548564
dc.internal.wokid WOS:000434641400007
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Seventh Framework Programme en
dc.contributor.funder FP7 People: Marie-Curie Actions en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Oncogene en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress r.oconnor@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/11/PI/1139/IE/IGF-I Receptor signalling and regulation/ en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/251480/EU/Identification of Clinically Useful Biomarkers for IGF-I Receptor Signalling n Cancer/BIOMARKERIGF en

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