dc.contributor.author | Oldrini, B | |
dc.contributor.author | Hsieh, W-Y | |
dc.contributor.author | Erdjument-Bromage, H | |
dc.contributor.author | Codega, P | |
dc.contributor.author | Carro, MS | |
dc.contributor.author | Curiel-García, A | |
dc.contributor.author | Campos, C | |
dc.contributor.author | Pourmaleki, M | |
dc.contributor.author | Grommes, C | |
dc.contributor.author | Vivanco, I | |
dc.contributor.author | Rohle, D | |
dc.contributor.author | Bielski, CM | |
dc.contributor.author | Taylor, BS | |
dc.contributor.author | Hollmann, TJ | |
dc.contributor.author | Rosenblum, M | |
dc.contributor.author | Tempst, P | |
dc.contributor.author | Blenis, J | |
dc.contributor.author | Squatrito, M | |
dc.contributor.author | Mellinghoff, IK | |
dc.date.accessioned | 2017-11-22T11:04:11Z | |
dc.date.issued | 2017-12-11 | |
dc.identifier.citation | Nature communications, 2017, 8 (1), pp. 2035 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/921 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-017-02185-w | |
dc.description.abstract | Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin β family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output. Focal deletions of the RanBP6 locus on chromosome 9p were found in a subset of glioblastoma (GBM) and silencing of RanBP6 promoted glioma growth in vivo. Our results provide an example of EGFR deregulation in cancer through silencing of components of the nuclear import pathway. | |
dc.format | Electronic | |
dc.format.extent | 2035 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cells, Cultured | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Mice, Knockout | |
dc.subject | Humans | |
dc.subject | Mice, SCID | |
dc.subject | Glioma | |
dc.subject | Doxorubicin | |
dc.subject | ran GTP-Binding Protein | |
dc.subject | beta Karyopherins | |
dc.subject | Antibiotics, Antineoplastic | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Active Transport, Cell Nucleus | |
dc.subject | Female | |
dc.subject | STAT3 Transcription Factor | |
dc.subject | Gene Knockdown Techniques | |
dc.subject | Feedback, Physiological | |
dc.subject | HEK293 Cells | |
dc.subject | ErbB Receptors | |
dc.title | EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-11-09 | |
rioxxterms.funder | The Institute of Cancer Research | |
rioxxterms.identifier.project | Unspecified | |
rioxxterms.versionofrecord | 10.1038/s41467-017-02185-w | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-12-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not 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 Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Addictions | |
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 Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Addictions | |
pubs.publication-status | Published | |
pubs.volume | 8 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Addictions | |
dc.contributor.icrauthor | Vivanco, Igor | |