Understanding cytoskeleton regulators in glioblastoma multiforme for therapy design.
The cellular cytoskeleton forms the primary basis through which a cell governs the changes in size, shape, migration, proliferation, and forms the primary means through which the cells respond to their environment. Indeed, cell and tissue morphologies are used routinely not only to grade tumors but also in various high-content screening methods with an aim to identify new small molecules with therapeutic potential. This study examines the expression of various cytoskeleton regulators in glioblastoma multiforme (GBM). GBM is a very aggressive disease with a low life expectancy even after chemo- and radiotherapy. Cancer cells of GBM are notorious for their invasiveness, ability to develop resistance to chemo- and radiotherapy, and to form secondary site tumors. This study aims to gain insight into cytoskeleton regulators in GBM cells and to understand the effect of various oncology drugs, including temozolomide, on cytoskeleton regulators. We compare the expression of various cytoskeleton regulators in GBM-derived tumor and normal tissue, CD133-postive and -negative cells from GBM and neural cells, and GBM stem-like and differentiated cells. In addition, the correlation between the expression of cytoskeleton regulators with the clinical outcome was examined to identify genes associated with longer patient survival. This was followed by a small molecule screening with US Food and Drug Administration (FDA)-approved oncology drugs, and its effect on cellular cytoskeleton was compared to treatment with temozolomide. This study identifies various groups of cytoskeletal regulators that have an important effect on patient survival and tumor development. Importantly, this work highlights the advantage of using cytoskeleton regulators as biomarkers for assessing prognosis and treatment design for GBM.
Department of Microbiology Tumor and Cell Biology.
Samaneh
S
Masoumi
Center for Hematology and Regenerative Medicine, Department of Medicine.
Aditya
A
Harisankar
Department of Neuroscience, Karolinska Institutet, Solna, Sweden.
Aileen
A
Gracias
Department of Microbiology Tumor and Cell Biology.
Fabian
F
Bachinger
Department of Microbiology Tumor and Cell Biology; Department of Neurosurgery, University Hospital, Leipzig, Germany.
Temesgen
T
Fufa
Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden.
Gayathri
G
Chandrasekar
Department of Neurosurgery, University Hospital, Leipzig, Germany.
Frank
F
Gaunitz
Center for Hematology and Regenerative Medicine, Department of Medicine.
Julian
J
Walfridsson
Department of Microbiology Tumor and Cell Biology.
Satish S
SS
Kitambi
GBM; Phenotypic Drug Discovery; actin; actomyosin; cytoskeleton; glioma; microtubules; tubulin
Clin Cancer Res. 2004 Dec 15;10 (24):8177-84
15623592
Lancet Oncol. 2009 May;10 (5):459-66
19269895
Anticancer Agents Med Chem. 2013 Sep;13(7):1057-68
23343081
Neurosurg Focus. 2006 Apr 15;20(4):E24
16709030
Carcinogenesis. 2015 Jul;36(7):748-56
25957251
EMBO J. 1997 Sep 1;16(17):5445-54
9312003
J Clin Oncol. 2004 May 1;22(9):1598-604
15117981
Nature. 2013 Feb 6;494(7438):506
23389443
Cancer Biol Med. 2015 Sep;12(3):223-37
26487967
EMBO J. 1996 Aug 1;15(15):3778-86
8670882
Oncoscience. 2014 Jan 01;1(1):39-48
25593987
Science. 2008 Sep 26;321(5897):1807-12
18772396
Cancer Lett. 2006 Jun 8;237(1):10-21
16002209
J Exp Clin Cancer Res. 2012 May 04;31:43
22559840
Cell. 2013 Oct 10;155(2):462-77
24120142
Neuro Oncol. 2012 Nov;14 Suppl 5:v1-49
23095881
Cell. 2014 Apr 10;157(2):313-28
24656405
Oncol Rep. 2015 Oct;34(4):1815-24
26238396
PLoS One. 2013 May 29;8(5):e64169
23734191
Front Oncol. 2013 Oct 04;3:241
24109588
J Pathol. 2012 Mar;226(4):666-73
21989536
J Neurooncol. 2015 Feb;121(3):425-31
25385572
Acta Neuropathol. 2007 Aug;114(2):97-109
17618441
PLoS One. 2008;3(10 ):e3507
18949047
Histopathology. 2012 Jul;61(1):78-87
22439598
Traffic. 2008 Dec;9(12):2221-35
18764928
Sci Signal. 2013 Apr 02;6(269):pl1
23550210
PLoS One. 2013 Nov 12;8(11):e78943
24265731
Oncogene. 2011 Aug 11;30(32):3537-48
21423202
Nature. 2008 Oct 23;455(7216):1061-8
18772890
Neurosurgery. 2011 Dec;69(6):1272-9; discussion 1279-80
21562434
PLoS One. 2015 Oct 30;10(10):e0141285
26517117
Cancer Discov. 2012 May;2(5):401-4
22588877
Neurochem Res. 2011 Aug;36(8):1397-406
21544552
N Engl J Med. 2005 Mar 10;352(10 ):997-1003
15758010
Oncology. 2012;83(1):1-9
22688083
Med Oncol. 2013 Mar;30(1):372
23315217
J Neurooncol. 2008 May;88(1):105-13
18283418
N Engl J Med. 2005 Mar 10;352(10 ):987-96
15758009
Cancer Metastasis Rev. 2009 Jun;28(1-2):15-33
19169796
Neurochem Res. 2007 Aug;32(8):1387-98
17406983
Annu Rev Biophys. 2008;37:65-95
18573073