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 |
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dc.contributor.author |
O'Flanagan, Ciara |
|
dc.contributor.author |
Addario, Barbara |
|
dc.contributor.author |
McCabe, Nuala |
|
dc.contributor.author |
Kennedy, Richard |
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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 |
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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 |