Please use this identifier to cite or link to this item:
10.1101/gad.300079.117
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DC Field | Value | Language |
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dc.contributor.author | Zanca, Ciro | - |
dc.contributor.author | Villa, Genaro R. | - |
dc.contributor.author | Benitez, Jorge A. | - |
dc.contributor.author | Thorne, Amy Haseley | - |
dc.contributor.author | Koga, Tomoyuki | - |
dc.contributor.author | D’Antonio, Matteo | - |
dc.contributor.author | Ikegami, Shiro | - |
dc.contributor.author | Ma, Jianhui | - |
dc.contributor.author | Boyer, Antonia D. | - |
dc.contributor.author | Banisadr, Afsheen | - |
dc.contributor.author | Jameson, Nathan M. | - |
dc.contributor.author | Parisian, Alison D. | - |
dc.contributor.author | Eliseeva, Olesja V. | - |
dc.contributor.author | Barnabe, Gabriela F. | - |
dc.contributor.author | Liu, Feng | - |
dc.contributor.author | Wu, Sihan | - |
dc.contributor.author | Yang, Huijun | - |
dc.contributor.author | Wykosky, Jill | - |
dc.contributor.author | Frazer, Kelly A. | - |
dc.contributor.author | Verkhusha, Vladislav V. | - |
dc.contributor.author | Isaguliants, Maria G. | - |
dc.contributor.author | Weiss, William A. | - |
dc.contributor.author | Gahman, Timothy C. | - |
dc.contributor.author | Shiau, Andrew K. | - |
dc.contributor.author | Chen, Clark C. | - |
dc.contributor.author | Mischel, Paul S. | - |
dc.contributor.author | Cavenee, Webster K. | - |
dc.contributor.author | Furnari, Frank B. | - |
dc.date.accessioned | 2021-06-15T09:40:01Z | - |
dc.date.available | 2021-06-15T09:40:01Z | - |
dc.date.issued | 2017-06-15 | - |
dc.identifier.citation | Zanca , C , Villa , G R , Benitez , J A , Thorne , A H , Koga , T , D’Antonio , M , Ikegami , S , Ma , J , Boyer , A D , Banisadr , A , Jameson , N M , Parisian , A D , Eliseeva , O V , Barnabe , G F , Liu , F , Wu , S , Yang , H , Wykosky , J , Frazer , K A , Verkhusha , V V , Isaguliants , M G , Weiss , W A , Gahman , T C , Shiau , A K , Chen , C C , Mischel , P S , Cavenee , W K & Furnari , F B 2017 , ' Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity ' , Genes and Development , vol. 31 , no. 12 , pp. 1212-1227 . https://doi.org/10.1101/gad.300079.117 | - |
dc.identifier.issn | 0890-9369 | - |
dc.identifier.uri | https://dspace.rsu.lv/jspui/handle/123456789/5031 | - |
dc.description | Funding Information: We thank Dr. David James, Dr. Frederick Lang, Dr. Cameron Brennan, and Dr. Harley Kornblum for GBM-PDX neurospheres. We thank Dr. Karen Arden for continuous support and critical evaluation of the results. We thank Dr. Robert Davis, Dr. German Gomez, Dr. Tiffany Taylor, Dr. Rachel Reed, Dr. Melissa Mcalonis, and Dr. Sora Lee for technical support. In memory of Rosa Lupo. This work was supported by the Defeat GBM Research Collaborative, a subsidiary of the National Brain Tumor Society (F.B.F. and P.S.M.), R01-NS080939 (F.B.F.), the James S. McDonnell Foundation (F.B.F.), the National Cancer Institute (2T32CA009523-29A1) (A.H.T), and 1RO1NS097649-01 (C.C.C.). C.Z. was partially supported by an American-Italian Cancer Foundation post-doctoral research fellowship. F.L. received a Gao Feng Gao Yuan Scholarship Award. T.C.G., A.K.S., P.S.M., W.K.C., and F.B.F. receive salary and additional support from the Ludwig Institute for Cancer Research. Publisher Copyright: © 2017 Zanca et al. | - |
dc.description.abstract | In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs). NF-κB and survivin are coordinately up-regulated in GBM patient tumors, and functional inhibition of either protein or BRD4 in in vitro and in vivo models restores sensitivity to EGFR TKIs. These results provide a rationale for improving anti-EGFR therapeutic efficacy through pharmacological uncoupling of a convergence point of NF-κB-mediated survival that is leveraged by an interclonal circuitry mechanism established by intratumoral mutational heterogeneity. | en |
dc.format.extent | 16 | - |
dc.format.extent | 10388410 | - |
dc.language.iso | eng | - |
dc.relation.ispartof | Genes and Development | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | EGFR | - |
dc.subject | Glioblastoma | - |
dc.subject | IL-6 | - |
dc.subject | NF-κB | - |
dc.subject | Survivin | - |
dc.subject | Tumor heterogeneity | - |
dc.subject | 1.6 Biological sciences | - |
dc.subject | 1.1. Scientific article indexed in Web of Science and/or Scopus database | - |
dc.subject | Genetics | - |
dc.subject | Developmental Biology | - |
dc.title | Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity | en |
dc.type | /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article | - |
dc.identifier.doi | 10.1101/gad.300079.117 | - |
dc.contributor.institution | Research Department | - |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85027005612&partnerID=8YFLogxK | - |
dc.description.status | Peer reviewed | - |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
Files in This Item:
File | Size | Format | |
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Glioblastoma_cellular_cross_talk_converges.pdf | 10.14 MB | Adobe PDF | View/Open |
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