TROY interacts with RKIP to promote glioma development

Xiujie Liu,Cheng He,Yong Zhang,Yi An,Jie Ma,Wei Meng,Jifeng Feng,Yinghui Bao,Ping Yang,Yingyan Pu,Jianfeng Zhou,Zhigang Liu,Yan Lu,Xiaofei Gao,Yujie Tang,Zhida Su

doi:10.1038/s41388-018-0503-x

Abstract

TROY is a component of the Nogo receptor complex and plays the key role in neuronal survival, migration, and differentiation. Here, we show the up-regulation of TROY in human glioma tissues and cells. Inhibition of TROY expression slowed glioma development in vivo and in vitro. Raf kinase inhibitor (RKIP) was found to interact with TROY. The physical interaction of TROY/RKIP was confirmed via co-immunoprecipitation (co-IP) assays. Furthermore, we found that the TROY/RKIP interaction was enhanced by fetal bovine serum (FBS) exposure, and TROY knockdown also led to down-regulation of NF-κB. Finally, disruption of the TROY/RKIP interaction using the TAT-TROY (234–371 aa) protein reduced the glioma development in xenografted mice. This suggests the TROY/RKIP interaction is a potential target for therapy of gliomas.

Highlights

The yearly worldwide incidence of primary brain tumors leads to about 7% of premature life span lost prior to the age of 70 [1,2,3,4]
We examined the correlation between levels of TROY and patient survival among different grades of glial tumor in the patient specimens from public database including The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data
Gene Expression Profiling Interactive Analysis revealed TROY was significantly overexpressed in human glioblastoma multiforme or brain lower grade glioma tissues compared to normal glial tissues (Fig. 1f)

Summary

Introduction

The yearly worldwide incidence of primary brain tumors leads to about 7% of premature life span lost prior to the age of 70 [1,2,3,4]. Gliomas are the most common among brain tumors. Gliomas are graded as I to IV according to atypia, mitoses, necrosis, and microvascular enrichment. High-grade gliomas are more aggressive and malignant, These authors contributed : Xiujie Liu, Yinghui Bao, Wei Meng, Ping Yang. TROY, or tumor necrosis factor receptor 19 (TNFRSF19), is an orphan receptor of the TNFR superfamily [10, 11]. TROY has been widely reported as a coreceptor which activates the RhoA and inhibits neurite outgrowth [12, 13]. TROY-knockout mice show the significant reduced neurite outgrowth inhibition in the presences of myelin-associated inhibitory factors [14, 15]

Methods

Results

Conclusion