Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6884
Título
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer
Autor(es)
Oldrini, Barbara CNIO | Hsieh, Wan-Ying | Erdjument-Bromage, Hediye | Codega, Paolo | Carro, Maria Stella | Curiel-García, Alvaro | Campos, Carl | Pourmaleki, Maryam | Grommes, Christian | Vivanco, Igor | Rohle, Daniel | Bielski, Craig M | Taylor, Barry S | Hollmann, Travis J | Rosenblum, Marc | Tempst, Paul | Blenis, John | Squatrito, Massimo CNIO | Mellinghoff, Ingo K
Fecha de publicación
2017
Cita
Nat Commun. 2017; 8(1): 2035.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Active Transport, Cell Nucleus | Animals | Antibiotics, Antineoplastic | Cell Line, Tumor | Cells, Cultured | Doxorubicin | ErbB Receptors | Feedback, Physiological | Female | Gene Knockdown Techniques | Glioma | HEK293 Cells | Humans | Mice, Knockout | Mice, SCID | STAT3 Transcription Factor | Xenograft Model Antitumor Assays | beta Karyopherins | ran GTP-Binding Protein | Gene Expression Regulation, Neoplastic
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