• English
    • العربية
  • العربية
  • Login
  • QU
  • QU Library
  •  Home
  • Communities & Collections
  • Help
    • Item Submission
    • Publisher policies
    • User guides
    • FAQs
  • About QSpace
    • Vision & Mission
View Item 
  •   Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Research Units
  • Biomedical Research Center
  • Biomedical Research Center Research
  • View Item
  • Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Research Units
  • Biomedical Research Center
  • Biomedical Research Center Research
  • View Item
  •      
  •  
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    PDGFRα depletion attenuates glioblastoma stem cells features by modulation of STAT3, RB1 and multiple oncogenic signals.

    Thumbnail
    View/Open
    PDGFRα depletion.pdf (4.140Mb)
    Date
    2016-06-17
    Author
    Cenciarelli, Carlo
    Marei, Hany E.
    Felsani, Armando
    Casalbore, Patrizia
    Sica, Gigliola
    Puglisi, Maria Ausiliatrice
    Cameron, Angus J.M.
    Olivi, Alessandro
    Mangiola, Annunziato
    ...show more authors ...show less authors
    Metadata
    Show full item record
    Abstract
    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.
    DOI/handle
    http://dx.doi.org/10.18632/oncotarget.10132
    http://hdl.handle.net/10576/4692
    Collections
    • Biomedical Research Center Research [‎800‎ items ]

    entitlement


    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Home

    Submit your QU affiliated work

    Browse

    All of Digital Hub
      Communities & Collections Publication Date Author Title Subject Type Language Publisher
    This Collection
      Publication Date Author Title Subject Type Language Publisher

    My Account

    Login

    Statistics

    View Usage Statistics

    About QSpace

    Vision & Mission

    Help

    Item Submission Publisher policiesUser guides FAQs

    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Video