TROY interacts with RKIP to promote glioma development

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

doi:10.1038/s41388-018-0503-x

TROY interacts with RKIP to promote glioma development

Oncogene. 2019 Feb;38(9):1544-1559. doi: 10.1038/s41388-018-0503-x. Epub 2018 Oct 18.

Authors

Xiujie Liu¹, Yinghui Bao², Wei Meng³, Ping Yang⁴, Yi An⁵, Jie Ma³, Yujie Tang⁶, Zhigang Liu⁷, Yan Lu⁸, Jianfeng Zhou⁸, Yong Zhang⁸, Jifeng Feng⁸, Xiaofei Gao⁸, Zhida Su⁸, Yingyan Pu⁸, Cheng He⁹

Affiliations

¹ Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, 200433, China. LXJ186517@126.com.
² Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200127, China.
³ Department of Pediatric Neurosurgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200092, P.R. China.
⁴ Instrumental Analysis Center, School of Pharmacy, Fudan University, Shanghai, 201203, China.
⁵ Department of Therapeutic Oncology, Yale University School of Medicine, New Haven, CT, USA.
⁶ Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University, School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P.R. China.
⁷ Department of Radiation Oncology; Phase 1 Clinical Trial Ward, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519001, China.
⁸ Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, 200433, China.
⁹ Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, 200433, China. chenghe@smmu.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Carcinogenesis / genetics*
Cell Line, Tumor
Cell Survival / genetics
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
Glioma / genetics*
Glioma / pathology
Humans
Mice
NF-kappa B / genetics
Phosphatidylethanolamine Binding Protein / genetics*
Receptors, Tumor Necrosis Factor / genetics*
Serum / chemistry
Signal Transduction
Xenograft Model Antitumor Assays

Substances

NF-kappa B
PEBP1 protein, human
Phosphatidylethanolamine Binding Protein
Receptors, Tumor Necrosis Factor
TNFRSF19 protein, human