Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities
High invasiveness and resistance to chemo- and radiotherapy of glioblastoma
multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment
strategies for preventing migration and invasion of GBM cells are needed. Using two
different migration assays, Western blotting, conventional and super-resolution
(dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTORinhibitor
PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922
and/or irradiation on the migration, expression of marker proteins, focal adhesions
and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly
differing in their invasive capacity. Both lines were found to be strikingly different
in morphology and migration behavior. The less invasive DK-MG cells maintained a
polarized morphology and migrated in a directionally persistent manner, whereas the
highly invasive SNB19 cells showed a multipolar morphology and migrated randomly.
Interestingly, a single dose of 2 Gy accelerated wound closure in both cell lines
without affecting their migration measured by single-cell tracking. PI-103 inhibited
migration of DK-MG (p53 wt, PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells
probably due to aberrant reactivation of the PI3K pathway in SNB19 cells treated
with PI-103. In contrast, NVP-AUY922 exerted strong anti-migratory effects in both
cell lines. Inhibition of cell migration was associated with massive morphological
changes and reorganization of the actin cytoskeleton. Our results showed a cell linespecific
response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude
that anti-migratory agents warrant further preclinical investigation as potential
therapeutics for treatment of GBM.
%0 Journal Article
%1 memmel2017migration
%A Memmel, Simon
%A Sisario, Dmitri
%A Zöller, Caren
%A Fiedler, Vanessa
%A Katzer, Astrid
%A Heiden, Robin
%A Becker, Nicholas
%A Eing, Lorenz
%A Ferreira, Fábio L.R.
%A Zimmermann, Heiko
%A Sauer, Markus
%A Flentje, Michael
%A Sukhorukov, Vladimir L.
%A Djuzenova, Cholpon S.
%D 2017
%J Oncotarget
%K sauer vladimir
%N 0
%P 45298–45310
%T Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities
%U https://doi.org/10.18632/oncotarget.16847
%V 8
%X High invasiveness and resistance to chemo- and radiotherapy of glioblastoma
multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment
strategies for preventing migration and invasion of GBM cells are needed. Using two
different migration assays, Western blotting, conventional and super-resolution
(dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTORinhibitor
PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922
and/or irradiation on the migration, expression of marker proteins, focal adhesions
and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly
differing in their invasive capacity. Both lines were found to be strikingly different
in morphology and migration behavior. The less invasive DK-MG cells maintained a
polarized morphology and migrated in a directionally persistent manner, whereas the
highly invasive SNB19 cells showed a multipolar morphology and migrated randomly.
Interestingly, a single dose of 2 Gy accelerated wound closure in both cell lines
without affecting their migration measured by single-cell tracking. PI-103 inhibited
migration of DK-MG (p53 wt, PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells
probably due to aberrant reactivation of the PI3K pathway in SNB19 cells treated
with PI-103. In contrast, NVP-AUY922 exerted strong anti-migratory effects in both
cell lines. Inhibition of cell migration was associated with massive morphological
changes and reorganization of the actin cytoskeleton. Our results showed a cell linespecific
response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude
that anti-migratory agents warrant further preclinical investigation as potential
therapeutics for treatment of GBM.
@article{memmel2017migration,
abstract = {High invasiveness and resistance to chemo- and radiotherapy of glioblastoma
multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment
strategies for preventing migration and invasion of GBM cells are needed. Using two
different migration assays, Western blotting, conventional and super-resolution
(dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTORinhibitor
PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922
and/or irradiation on the migration, expression of marker proteins, focal adhesions
and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly
differing in their invasive capacity. Both lines were found to be strikingly different
in morphology and migration behavior. The less invasive DK-MG cells maintained a
polarized morphology and migrated in a directionally persistent manner, whereas the
highly invasive SNB19 cells showed a multipolar morphology and migrated randomly.
Interestingly, a single dose of 2 Gy accelerated wound closure in both cell lines
without affecting their migration measured by single-cell tracking. PI-103 inhibited
migration of DK-MG (p53 wt, PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells
probably due to aberrant reactivation of the PI3K pathway in SNB19 cells treated
with PI-103. In contrast, NVP-AUY922 exerted strong anti-migratory effects in both
cell lines. Inhibition of cell migration was associated with massive morphological
changes and reorganization of the actin cytoskeleton. Our results showed a cell linespecific
response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude
that anti-migratory agents warrant further preclinical investigation as potential
therapeutics for treatment of GBM.},
added-at = {2017-04-07T11:09:01.000+0200},
author = {Memmel, Simon and Sisario, Dmitri and Zöller, Caren and Fiedler, Vanessa and Katzer, Astrid and Heiden, Robin and Becker, Nicholas and Eing, Lorenz and Ferreira, Fábio L.R. and Zimmermann, Heiko and Sauer, Markus and Flentje, Michael and Sukhorukov, Vladimir L. and Djuzenova, Cholpon S.},
biburl = {https://www.bibsonomy.org/bibtex/24f792ec6e0dbcbc2eb1026676e85a7ba/reichert},
interhash = {a0563b5a24aa6f31a01aa8eeecb45b86},
intrahash = {4f792ec6e0dbcbc2eb1026676e85a7ba},
issn = {1949-2553},
journal = {Oncotarget},
keywords = {sauer vladimir},
month = {April},
number = 0,
pages = {45298–45310},
timestamp = {2018-06-14T12:14:56.000+0200},
title = {Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities},
url = {https://doi.org/10.18632/oncotarget.16847},
volume = 8,
year = 2017
}