Targeting dual specificity protein kinase TTK attenuates tumorigenesis of glioblastoma

// Jia Wang 1 , Yuchen Xie 2 , Xiaobin Bai 1 , Ning Wang 1 , Hai Yu 1, 2 , Zhong Deng 1, 2 , Minxue Lian 1 , Shuo Yu 2 , Hao Liu 1 , Wanfu Xie 1 and Maode Wang 1 1 Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China 2 School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China Correspondence to: Wanfu Xie, email: wanfu67@aliyun.com Maode Wang, email: maodewang@163.com Keywords: glioma stem-like cells; glioblastoma; TTK; MTFR2 Received: June 15, 2017      Accepted: November 21, 2017      Published: December 11, 2017 ABSTRACT Accumulating evidence has proved that glioma stem-like cells (GSCs) are responsible for tumorigenesis, treatment resistance, and subsequent tumor recurrence in glioblastoma (GBM). In this study, we identified dual specificity protein kinase TTK (TTK) as the most up-regulated and differentially expressed kinase encoding genes in GSCs. Functionally, TTK was essential for in vitro clonogenicity and in vivo tumor propagation in GSCs. Clinically, TTK expression was highly enriched in GBM, moreover, was inversely correlated with a poor prognosis in GBM patients. Mechanistically, mitochondrial fission regulator 2 (MTFR2) was identified as one of the most correlated genes to TTK and transcriptionally regulated TTK expression via activation of TTK promoter. Collectively, MTFR2-dependent regulation of TTK plays a key role in maintaining GSCs in GBM and is a potential novel druggable target for GBM.