2026-06-14T00:27:49Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68842024-11-29T21:44:50Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Oldrini, Barbara
author
Hsieh, Wan-Ying
author
Erdjument-Bromage, Hediye
author
Codega, Paolo
author
Carro, Maria Stella
author
Curiel-García, Alvaro
author
Campos, Carl
author
Pourmaleki, Maryam
author
Grommes, Christian
author
Vivanco, Igor
author
Rohle, Daniel
author
Bielski, Craig M
author
Taylor, Barry S
author
Hollmann, Travis J
author
Rosenblum, Marc
author
Tempst, Paul
author
Blenis, John
author
Squatrito, Massimo
author
Mellinghoff, Ingo K
funder
National Institutes of Health (Estados Unidos)
funder
Geoffrey Beene Foundation
funder
Fundación Seve Ballesteros
funder
Memorial Sloan Kettering Cancer Center
2018-12-18T12:37:50Z
2018-12-18T12:37:50Z
2017
Nat Commun. 2017; 8(1): 2035.
10.1038/s41467-017-02185-w
2041-1723
2041-1723
Nature communications
29229958
http://hdl.handle.net/20.500.12105/6884
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.
eng
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer
journal article
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