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@ARTICLE{Koch:819805,
author = {Koch, Katharina and Hartmann, Rudolf and Schröter,
Friederike and Kora Suwala, Abigail and Maciaczyk, Donata
and Caroline Krüger, Andrea and Willbold, Dieter and
Dietrich Kahlert, Ulf and Maciaczyk, Jaroslaw},
title = {{R}eciprocal regulation of the cholinic phenotype and
epithelial-mesenchymal transition in glioblastoma cells},
journal = {OncoTarget},
volume = {7},
number = {45},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {FZJ-2016-05400},
pages = {73414-73431},
year = {2016},
abstract = {Glioblastoma (GBM) is the most malignant brain tumor with
very limited therapeutic options. Standard multimodal
treatments, including surgical resection and combined
radio-chemotherapy do not target the most aggressive subtype
of glioma cells, brain tumor stem cells (BTSCs). BTSCs are
thought to be responsible for tumor initiation, progression,
and relapse. Furthermore, they have been associated with the
expression of mesenchymal features as a result of
epithelial-mesenchymal transition (EMT) thereby inducing
tumor dissemination and chemo resistance. Using high
resolution proton nuclear magnetic resonance spectroscopy
(1H NMR) on GBM cell cultures we provide evidence that the
expression of well-known EMT activators of the ZEB, TWIST
and SNAI families and EMT target genes N-cadherin and
VIMENTIN is associated with aberrant choline metabolism. The
cholinic phenotype is characterized by high intracellular
levels of phosphocholine and total choline derivatives and
was associated with malignancy in various cancers. Both
genetic and pharmacological inhibition of the cardinal
choline metabolism regulator choline kinase alpha (CHKα)
significantly reduces the cell viability, invasiveness,
clonogenicity, and expression of EMT associated genes in GBM
cells. Moreover, in some cell lines synergetic cytotoxic
effects were observed when combining the standard of care
chemotherapeutic temozolomide with the CHKα inhibitor
V-11-0711. Taken together, specific inhibition of the
enzymatic activity of CHKα is a powerful strategy to
suppress EMT which opens the possibility to target
chemo-resistant BTSCs through impairing their mesenchymal
transdifferentiation. Moreover, the newly identified
EMT-oncometabolic network may be helpful to monitor the
invasive properties of glioblastomas and the success of
anti-EMT therapy.},
cin = {ICS-6},
ddc = {610},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000387452100075},
doi = {10.18632/oncotarget.12337},
url = {https://juser.fz-juelich.de/record/819805},
}