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@ARTICLE{Phillips:130329,
author = {E. Phillips$^*$ and V. Lang$^*$ and J. Bohlen$^*$ and F.
Bethke$^*$ and L. Puccio$^*$ and D. Tichy$^*$ and C.
Herold-Mende$^*$ and T. Hielscher$^*$ and P. Lichter$^*$ and
V. Goidts$^*$},
title = {{T}argeting atypical protein kinase {C} iota reduces
viability in glioblastoma stem-like cells via a notch
signaling mechanism.},
journal = {International journal of cancer},
volume = {139},
number = {8},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2017-05408},
pages = {1776 - 1787},
year = {2016},
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.},
keywords = {Isoenzymes (NLM Chemicals) / Protein Kinase Inhibitors (NLM
Chemicals) / Receptors, Notch (NLM Chemicals) / Protein
Kinase C (NLM Chemicals) / protein kinase C lambda (NLM
Chemicals)},
cin = {B067 / B060 / C060},
ddc = {610},
cid = {I:(DE-He78)B067-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)C060-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27299852},
doi = {10.1002/ijc.30234},
url = {https://inrepo02.dkfz.de/record/130329},
}