دورية أكاديمية
Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition
| العنوان: | Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition |
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| المؤلفون: | Elisa Oppici, Ilaria Dando, Elena Butturini, Elisa Dalla Pozza, Mercedes Nadal-Serrano, Jordi Oliver, Pilar Roca, Sofia Mariotto, Barbara Cellini, Giovanni Blandino, Marta Palmieri, Silvia Di Agostino, Massimo Donadelli, Cordani, Marco |
| بيانات النشر: | FEBS PRESS |
| سنة النشر: | 2016 |
| المجموعة: | Universidad Complutense de Madrid (UCM): E-Prints Complutense |
| مصطلحات موضوعية: | 616-006.04, Autophagy, Mutant p53, Gain-of-function, Cancer, mTOR, AMPK, Oncología, 3207 Patología |
| الوصف: | This work was supported by Italian Association for Cancer Research (AIRC)-Fondazione CariPaRo, Padova, Italy (n. C98C13000210007); Joint Projects program 2015 from University of Verona to M. Donadelli (n. B12I15002320003); Italian Association for Cancer Research (AIRC) to S. Di Agostino (AIRC IG-n.16984) and to G. Blandino (AIRC IG-n.14455). M. NadalSerrano was supported by a short-term fellowship for the stay abroad (University of Verona, Italy) from European Molecular Biology Organization (EMBO). I. Dando is a fellow of AIRC (AIRC-Fondazione CariPaRo, Padova, Italy) and NanoMedicine (Fondazione Cariverona, Project Verona Nanomedicine Initiative). E. Dalla Pozza is a fellow of ARC-Net (Applied Research on Cancer Network), University of Verona, Italy. E. Butturini is a fellow of Joint Project (University of Verona, Italy and Aboca, Sansepolcro, Arezzo, Italy). ; Mutations in TP53 gene play a pivotal role in tumorigenesis and cancer development. Here, we report that gain-of-function mutant p53 proteins inhibit the autophagic pathway favoring antiapoptotic effects as well as proliferation of pancreas and breast cancer cells. We found that mutant p53 significantly counteracts the formation of autophagic vesicles and their fusion with lysosomes throughout the repression of some key autophagy-related proteins and enzymes as BECN1 (and P-BECN1), DRAM1, ATG12, SESN1/2 and P-AMPK with the concomitant stimulation of mTOR signaling. As a paradigm of this mechanism, we show that atg12 gene repression was mediated by the recruitment of the p50 NF-κB/mutant p53 protein complex onto the atg12 promoter. Either mutant p53 or p50 NF-κB depletion downregulates atg12 gene expression. We further correlated the low expression levels of autophagic genes (atg12, becn1, sesn1, and dram1) with a reduced relapse free survival (RFS) and distant metastasis free survival (DMFS) of breast cancer patients carrying TP53 gene mutations conferring a prognostic value to this mutant p53-and autophagy-related signature. Interestingly, the mutant ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://hdl.handle.net/20.500.14352/94638Test; http://dx.doi.org/10.1016/j.molonc.2016.04.001Test. |
| DOI: | 10.1016/j.molonc.2016.04.001 |
| الإتاحة: | https://doi.org/20.500.14352/94638Test https://doi.org/10.1016/j.molonc.2016.04.001Test https://hdl.handle.net/20.500.14352/94638Test |
| حقوق: | restricted access |
| رقم الانضمام: | edsbas.20FFD2C6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.molonc.2016.04.001 |
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