Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein

    Access Status
    Fulltext not available
    Authors
    Daniel, P.
    Filiz, G.
    Brown, D.
    Christie, M.
    Waring, P.
    Zhang, Y.
    Haynes, J.
    Pouton, C.
    Flanagan, D.
    Vincan, Elizabeth
    Johns, T.
    Montgomery, K.
    Phillips, W.
    Mantamadiotis, T.
    Date
    2018
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Daniel, P. and Filiz, G. and Brown, D. and Christie, M. and Waring, P. and Zhang, Y. and Haynes, J. et al. 2018. PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein. Neuro-Oncology. 20 (10): pp. 1344-1355.
    Source Title
    Neuro-Oncology
    DOI
    10.1093/neuonc/noy068
    ISSN
    1522-8517
    School
    School of Pharmacy and Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/71836
    Collection
    • Curtin Research Publications
    Abstract

    © The Author(s) 2018. Background. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling is common in cancers, but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells (NSPCs), where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. Methods. To investigate the role of the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, phosphatase and tensin homolog (PTEN), to NSPCs. Results. Expression of a Pik3caH1047A was sufficient to generate tumors with oligodendroglial features, but simultaneous loss of PTEN was required for the development of invasive, high-grade glioma. Pik3caH1047A-PTEN mutant NSPCs exhibited enhanced neurosphere formation which correlated with increased Wnt signaling, while loss of cAMP response element binding protein (CREB) in Pik3caH1047A-Pten mutant tumors led to longer symptom-free survival in mice. Conclusion. Taken together, our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis and that disruption of downstream CREB signaling attenuates tumor expansion.

    Related items

    Showing items related by title, author, creator and subject.

    • Intestinal epithelial-specific PTEN inactivation results in tumor formation
      Byun, D.; Ahmed, N.; Nasser, S.; Shin, J.; Al-Obaidi, S.; Goel, S.; Corner, G.; Wilson, A.; Flanagan, D.; Williams, D.; Augenlicht, L.; Vincan, Elizabeth; Mariadason, J. (2011)
      Intestinal epithelial-specific PTEN inactivation results in tumor formation. Am J Physiol Gastrointest Liver Physiol 301: G856-G864, 2011. First published August 11, 2011; doi:10.1152/ajpgi.00178.2011.-Phosphates and ...
    • Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), increases chemotherapeutic response of glioma stem-like cells
      Warrier, S.; Balu, S.; Kumar, Alan Prem; Michael, M.; Dharmarajan, Arunasalam (2014)
      Malignant gliomas have a highly tumorigenic subpopulation, termed cancer stem cells (CSCs), that drives tumor formation and proliferation. CSCs possess inherent resistance mechanisms against radiation- and chemotherapy- ...
    • Targeting PDK1 in cancer
      Raimondi, C.; Falasca, Marco (2011)
      Abnormal activation of phosphoinositide 3-kinase (PI3K) signalling is very common in cancer, leading to deregulation of several intracellular processes normally controlled by this enzyme, including cell survival, growth, ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.