TY  - JOUR
A1  - Jungwirth, Gerhard
A1  - Yu, Tao
A1  - Moustafa, Mahmoud
A1  - Rapp, Carmen
A1  - Warta, Rolf
A1  - Jungk, Christine
A1  - Sahm, Felix
A1  - Dettling, Steffen
A1  - Zweckberger, Klaus
A1  - Lamszus, Katrin
A1  - Senft, Christian
A1  - Loehr, Mario
A1  - Keßler, Almuth F.
A1  - Ketter, Ralf
A1  - Westphal, Manfred
A1  - Debus, Juergen
A1  - von Deimling, Andreas
A1  - Simon, Matthias
A1  - Unterberg, Andreas
A1  - Abdollahi, Amir
A1  - Herold-Mende, Christel
T1  - Identification of KIF11 as a Novel Target in Meningioma
JF  - Cancers
N2  - Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas.
KW  - meningioma
KW  - KIF
KW  - kinesin
KW  - KIF11
KW  - NCH93
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197402
SN  - 2072-6694
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Wolter, Patrick
A1  - Hanselmann, Steffen
A1  - Pattschull, Grit
A1  - Schruf, Eva
A1  - Gaubatz, Stefan
T1  - Central spindle proteins and mitotic kinesins are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cell lines and are potential targets for therapy
JF  - Oncotarget
N2  - The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1. We demonstrate that six mitotic kinesins and two microtubule-associated non-motor proteins (MAPs) CEP55 and PRC1 are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cells.
Suppression of KIF23 and PRC1 strongly suppressed proliferation of MDA-MB-231 cells. The set of MMB-FOXM1 regulated kinesins genes and 4 additional kinesins which we referred to as the mitotic kinesin signature (MKS) is linked to poor outcome in breast cancer patients. Thus, mitotic kinesins could be used as prognostic biomarker and could be potential therapeutic targets for the treatment of breast cancer.
KW  - breast cancer
KW  - kinesin
KW  - cell cycle
KW  - cytokinesis
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171851
VL  - 8
IS  - 7
ER  -