دورية أكاديمية
PDGFRα depletion attenuates glioblastoma stem cells features by modulation of STAT3, RB1 and multiple oncogenic signals
| العنوان: | PDGFRα depletion attenuates glioblastoma stem cells features by modulation of STAT3, RB1 and multiple oncogenic signals |
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| المؤلفون: | Cenciarelli, Carlo, Marei, Hany E., Felsani, Armando, Casalbore, Patrizia, Sica, Gigliola, Puglisi, Maria Ausiliatrice, Cameron, Angus J. M., Olivi, Alessandro, Mangiola, Annunziato |
| المساهمون: | Cenciarelli, Carlo, Marei, Hany E., Felsani, Armando, Casalbore, Patrizia, Sica, Gigliola, Puglisi, Maria Ausiliatrice, Cameron, Angus J. M., Olivi, Alessandro, Mangiola, Annunziato |
| سنة النشر: | 2016 |
| المجموعة: | ARUd'A - Archivio Istituzionale della ricerca dell'università Chieti-Pescara (IRIS) |
| مصطلحات موضوعية: | Cancer stem cell, Glioblastoma, PDGFRa, RB1, STAT3, Adult, Brain Neoplasm, Carcinogenesi, Cell Differentiation, Cell Proliferation, Cells, Cultured, Gene Expression Regulation, Neoplastic, Human, Neoplastic Stem Cell, Phosphorylation, Platelet-Derived Growth Factor, RNA Interference, Receptor, Platelet-Derived Growth Factor alpha, Retinoblastoma Binding Protein, STAT3 Transcription Factor, Signal Transduction, Ubiquitin-Protein Ligase, Oncology |
| الوصف: | Platelet derived growth factor receptors (PDGFRs) play an important role in tumor pathogenesis, and they are frequently overexpressed in glioblastoma (GBM). Earlier we have shown a higher protein expression of PDGFR isoforms (α and β) in peritumoral-tissue derived cancer stem cells (p-CSC) than in tumor core (c-CSC) of several GBM affected patients. In the current study, in order to assess the activity of PDGFRα/PDGF-AA signaling axis, we performed time course experiments to monitor the effects of exogenous PDGF-AA on the expression of downstream target genes in c-CSC vs p-CSC. Interestingly, in p-CSC we detected the upregulation of Y705-phosphorylated Stat3, concurrent with a decrement of Rb1 protein in its active state, within minutes of PDGF-AA addition. This finding prompted us to elucidate the role of PDGFRα in self-renewal, invasion and differentiation in p-CSC by using short hairpin RNA depletion of PDGFRα expression. Notably, in PDGFRα-depleted cells, protein analysis revealed attenuation of stemness-related and glial markers expression, alongside early activation of the neuronal marker MAP2a/b that correlated with the induction of tumor suppressor Rb1. The in vitro reduction of the invasive capacity of PDGFRα-depleted CSC as compared to parental cells correlated with the downmodulation of markers of epithelial-mesenchymal transition phenotype and angiogenesis. Surprisingly, we observed the induction of anti-apoptotic proteins and compensatory oncogenic signals such as EDN1, EDNRB, PRKCB1, PDGF-C and PDGF-D. To conclude, we hypothesize that the newly discovered PDGFRα/Stat3/Rb1 regulatory axis might represent a potential therapeutic target for GBM treatment. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27344175; info:eu-repo/semantics/altIdentifier/wos/WOS:000385433000034; volume:7; issue:33; firstpage:53047; lastpage:53063; numberofpages:17; journal:ONCOTARGET; http://hdl.handle.net/11564/700291Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84982311549; https://www.oncotarget.com/article/10132/textTest/ |
| DOI: | 10.18632/oncotarget.10132 |
| الإتاحة: | https://doi.org/10.18632/oncotarget.10132Test http://hdl.handle.net/11564/700291Test https://www.oncotarget.com/article/10132/textTest/ |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E3000B56 |
| قاعدة البيانات: | BASE |
| DOI: | 10.18632/oncotarget.10132 |
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