FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion
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.contributor.funder | Science Foundation Ireland | en |
dc.contributor.funder | Seventh Framework Programme | en |
dc.contributor.funder | FP7 People: Marie-Curie Actions | en |
dc.date.accessioned | 2018-11-09T12:00:40Z | |
dc.date.available | 2018-11-09T12:00:40Z | |
dc.date.issued | 2018-03-15 | |
dc.date.updated | 2018-11-09T08:42:14Z | |
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.description.status | Peer reviewed | en |
dc.description.version | Accepted Version | en |
dc.format.mimetype | application/pdf | en |
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.doi | 10.1038/s41388-017-0113-z | |
dc.identifier.endpage | 3150 | en |
dc.identifier.issn | 0950-9232 | |
dc.identifier.journaltitle | Oncogene | en |
dc.identifier.startpage | 3131 | en |
dc.identifier.uri | http://hdl.handle.net/10468/7082 | |
dc.identifier.volume | 37 | en |
dc.language.iso | en | en |
dc.publisher | Springer Nature | 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 |
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 |