2026-06-14T03:28:51Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/68842024-11-29T21:44:50Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2017 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. 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 EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer