دورية أكاديمية
URI is an oncogene amplified in ovarian cancer cells and is required for their survival.
| العنوان: | URI is an oncogene amplified in ovarian cancer cells and is required for their survival. |
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| المؤلفون: | Theurillat, Jean-Philippe, Metzler, Stefan Christian, Henzi, Nico, Djouder, Nabil, Helbling, Marianne, Zimmermann, Anna-Kathrin, Jacob, Francis, Soltermann, Alex, Caduff, Rosmarie, Heinzelmann-Schwarz, Viola, Moch, Holger, Krek, Wilhelm |
| المساهمون: | Gertrud-Hagmann-Stiftung fur Malignomforschung, Swiss Cancer League, Julius Muller Stiftung zur Unterstutzung der Krebsforschung |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2011 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | Gene Amplification, Animals, Cell Line, Tumor, Cell Survival, Female, Gene Expression Regulation, Neoplastic, HeLa Cells, Humans, Immunoblotting, Immunohistochemistry, In Situ Hybridization, Fluorescence, Intracellular Signaling Peptides and Proteins, Kaplan-Meier Estimate, Mice, Nude, Neoplasms, Experimental, Oncogene Proteins, Ovarian Neoplasms, Protein Binding, Protein Phosphatase 1, RNA Interference, Repressor Proteins, Ribosomal Protein S6 Kinases, Transplantation, Heterologous, Tumor Burden |
| الوصف: | Abrogation of negative feedback control represents a fundamental requirement for aberrantly activated signaling pathways to promote malignant transformation and resistance to therapy. Here we identify URI, which encodes a mitochondrial inhibitor of PP1γ and PP1γ-mediated feedback inhibition of S6K1-BAD survival signaling, as an oncogene amplified and overexpressed in ovarian cancer cell lines and human ovarian carcinomas. URI is an "addicting" oncogene selectively required for the survival of ovarian cancer cells with increased URI copy number. By constitutively detaining PP1γ in inactive complexes, URI sustains S6K1 survival signaling under growth factor-limiting conditions and mediates resistance of cells to cisplatin. Thus, oncogenic activation of URI defines an important mechanism for activating mitochondrial S6K1-BAD signaling and promoting cell survival through disabling PP1γ-dependent negative feedback inhibition. ; We thank all members of the laboratories for helpful discussions. We also thank Stefan Neuenschwander from the Functional Genomics Center Zurich, for the analysis of the SNP-array data, and T. Rudolph, S. Behnke, and M. Storz for skillful technical assistance. We thank the Tissue Tumor Bank of the University Hospital Zurich for providing tissues. J.P.T. is funded by the Gertrud-Hagmann-Stiftung fur Malignomforschung arranged by the Swiss Group for Clinical Cancer Research, by a grant from the Swiss Cancer League (KLS-02014-02-2007), and by the Julius Muller Stiftung zur Unterstutzung der Krebsforschung. ; Sí |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 21397856 1878-3686 |
| العلاقة: | https://doi.org/10.1016/j.ccr.2011.01.019Test.; Cancer Cell. 2011;19(3):317-32.; http://hdl.handle.net/20.500.12105/17543Test; Cancer cell |
| DOI: | 10.1016/j.ccr.2011.01.019 |
| الإتاحة: | https://doi.org/20.500.12105/17543Test https://doi.org/10.1016/j.ccr.2011.01.019Test https://hdl.handle.net/20.500.12105/17543Test |
| حقوق: | http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.635EA105 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 21397856 18783686 |
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| DOI: | 10.1016/j.ccr.2011.01.019 |