دورية أكاديمية
Fibroblast growth factor receptors as novel therapeutic targets in SNF5-deleted malignant rhabdoid tumors.
| العنوان: | Fibroblast growth factor receptors as novel therapeutic targets in SNF5-deleted malignant rhabdoid tumors. |
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| المؤلفون: | Simon Wöhrle, Andreas Weiss, Moriko Ito, Audrey Kauffmann, Masato Murakami, Zainab Jagani, Anne Thuery, Beatrice Bauer-Probst, Flavia Reimann, Christelle Stamm, Astrid Pornon, Vincent Romanet, Vito Guagnano, Thomas Brümmendorf, William R Sellers, Francesco Hofmann, Charles W M Roberts, Diana Graus Porta |
| المصدر: | PLoS ONE, Vol 8, Iss 10, p e77652 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers arising in brain, kidney and soft tissues, which are characterized by loss of the tumor suppressor SNF5/SMARCB1. MRTs are poorly responsive to chemotherapy and thus a high unmet clinical need exists for novel therapies for MRT patients. SNF5 is a core subunit of the SWI/SNF chromatin remodeling complex which affects gene expression by nucleosome remodeling. Here, we report that loss of SNF5 function correlates with increased expression of fibroblast growth factor receptors (FGFRs) in MRT cell lines and primary tumors and that re-expression of SNF5 in MRT cells causes a marked repression of FGFR expression. Conversely, siRNA-mediated impairment of SWI/SNF function leads to elevated levels of FGFR2 in human fibroblasts. In vivo, treatment with NVP-BGJ398, a selective FGFR inhibitor, blocks progression of a murine MRT model. Hence, we identify FGFR signaling as an aberrantly activated oncogenic pathway in MRTs and propose pharmacological inhibition of FGFRs as a potential novel clinical therapy for MRTs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC3813701?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0077652 |
| URL الوصول: | https://doaj.org/article/5ddabf7e37d840fe9ce647ad449900b5 |
| رقم الأكسشن: | edsdoj.5ddabf7e37d840fe9ce647ad449900b5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0077652 |