Identification of KIF11 as a novel target in meningioma

  • 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.

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Author:Gerhard JungwirthORCiDGND, Tao Yu, Mahmoud Moustafa, Carmen Rapp, Rolf WartaORCiDGND, Christine Jungk, Felix Sahm, Steffen Dettling, Klaus Zweckberger, Katrin Lamszus, Christian SenftORCiDGND, Mario Loehr, Almuth F. Keßler, Ralf Ketter, Manfred Westphal, Jürgen Debus, Andreas von Deimling, Matthias Simon, Andreas Unterberg, Amir AbdollahiORCiDGND, Christel Herold-MendeORCiDGND
Parent Title (English):Cancers
Place of publication:Basel
Document Type:Article
Date of Publication (online):2019/04/15
Date of first Publication:2019/04/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/10/22
Tag:KIF; KIF11; NCH93; kinesin; meningioma
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0