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Status: Bibliographieeintrag

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Verfasst von:Phillips, Emma [VerfasserIn]   i
 Lang, Verena [VerfasserIn]   i
 Bohlen, Jonathan [VerfasserIn]   i
 Bethke, Frederic [VerfasserIn]   i
 Puccio, Laura [VerfasserIn]   i
 Tichy, Diana [VerfasserIn]   i
 Herold-Mende, Christel [VerfasserIn]   i
 Hielscher, Thomas [VerfasserIn]   i
 Lichter, Peter [VerfasserIn]   i
 Goidts, Violaine [VerfasserIn]   i
Titel:Targeting atypical protein kinase C iota reduces viability in glioblastoma stem-like cells via a notch signaling mechanism
Verf.angabe:Emma Phillips, Verena Lang, Jonathan Bohlen, Frederic Bethke, Laura Puccio, Diana Tichy, Christel Herold‐Mende, Thomas Hielscher, Peter Lichter and Violaine Goidts
E-Jahr:2016
Jahr:15 October 2016
Umfang:12 S.
Titel Quelle:Enthalten in: International journal of cancer
Ort Quelle:Bognor Regis : Wiley-Liss, 1966
Jahr Quelle:2016
Band/Heft Quelle:139(2016), 8, Seite 1776-1787
ISSN Quelle:1097-0215
Abstract:In a previous study, Protein Kinase C iota (PRKCI) emerged as an important candidate gene for glioblastoma (GBM) stem-like cell (GSC) survival. Here, we show that PKCι is overexpressed and activated in patient derived GSCs compared with normal neural stem cells and normal brain lysate, and that silencing of PRKCI in GSCs causes apoptosis, along with loss of clonogenicity and reduced proliferation. Notably, PRKCI silencing reduces tumor growth in vivo in a xenograft mouse model. PKCι has been intensively studied as a therapeutic target in non-small cell lung cancer, resulting in the identification of an inhibitor, aurothiomalate (ATM), which disrupts the PKCι/ERK signaling axis. However, we show that, although sensitive to pharmacological inhibition via a pseudosubstrate peptide inhibitor, GSCs are much less sensitive to ATM, suggesting that PKCι acts along a different signaling axis in GSCs. Gene expression profiling of PRKCI-silenced GSCs revealed a novel role of the Notch signaling pathway in PKCι mediated GSC survival. A proximity ligation assay showed that Notch1 and PKCι are in close proximity in GSCs. Targeting PKCι in the context of Notch signaling could be an effective way of attacking the GSC population in GBM.
DOI:doi:10.1002/ijc.30234
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1002/ijc.30234
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.30234
 DOI: https://doi.org/10.1002/ijc.30234
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:atypical protein kinase C iota
 glioblastoma
 glioblastoma stem-like cells
 notch signaling
K10plus-PPN:173604012X
Verknüpfungen:→ Zeitschrift

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