Identification of KIF11 as a Novel Target in Meningioma
Open Access
- 15 April 2019
- Vol. 11 (4), 545
- https://doi.org/10.3390/cancers11040545
Abstract
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.This publication has 88 references indexed in Scilit:
- Kinesin KIFC1 actively transports bare double-stranded DNANucleic Acids Research, 2013
- Impaired survival and long-term neurological problems in benign meningiomaNeuro-Oncology, 2012
- α3β1 integrin promotes radiation-induced migration of meningioma cellsInternational Journal of Oncology, 2011
- Mitotic Count, Brain Invasion, and Location Are Independent Predictors of Recurrence-Free Survival in Primary Atypical and Malignant Meningiomas: A Study of 86 PatientsNeurosurgery, 2010
- How kinesin motor proteins drive mitotic spindle function: Lessons from molecular assaysSeminars in Cell & Developmental Biology, 2010
- A phase I study of ispinesib, a kinesin spindle protein inhibitor, administered weekly for three consecutive weeks of a 28-day cycle in patients with solid tumorsInvestigational New Drugs, 2010
- A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumoursBritish Journal of Cancer, 2008
- Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neckInvestigational New Drugs, 2007
- A phase II study of ispinesib (SB-715992) in patients with metastatic or recurrent malignant melanoma: a National Cancer Institute of Canada Clinical Trials Group trialInvestigational New Drugs, 2007
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007