胶质瘤特异性PTPRZ1-MET融合蛋白导致MET癌蛋白表达增强及磷酸化

Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions.

作者信息

Chen Hui-Min, Yu Kai, Tang Xiao-yan, Bao Zhao-shi, Jiang Tao, Fan Xiao-Long, Chen Xiao-Wei, Su Xiao-Dong

机构信息

Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China; School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.

Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.

出版信息

FEBS Lett. 2015 Jun 4;589(13):1437-43. doi: 10.1016/j.febslet.2015.04.032. Epub 2015 Apr 29.

DOI:10.1016/j.febslet.2015.04.032

PMID:25935522

Abstract

PTPRZ1-MET (ZM) proteins are a group of fusion proteins identified in human gliomas by high-throughput transcriptome sequencing. ZM fusions are associated with poor prognosis in afflicted glioma patients and mediate oncogenic effects in assays. In this study, we show that ZM-carrying patients have increased hepatocyte growth factor receptor (MET) mRNA expression levels induced by fusion with receptor-type tyrosine-protein phosphatase zeta (PTPRZ1). Furthermore, ZM fusions preserve fundamental properties of wild-type MET with respect to processing and dimerization, and enhance phosphorylation in an hepatocyte growth factor (HGF)-dependent and independent manner. Our findings suggest that ZM induces gliomas through elevated expression and phosphorylation of the MET oncoprotein.

摘要

PTPRZ1-MET（ZM）蛋白是通过高通量转录组测序在人类胶质瘤中鉴定出的一组融合蛋白。ZM融合与患胶质瘤患者的不良预后相关，并在实验中介导致癌作用。在本研究中，我们发现携带ZM的患者因与受体型酪氨酸蛋白磷酸酶ζ（PTPRZ1）融合而导致肝细胞生长因子受体（MET）mRNA表达水平升高。此外，ZM融合保留了野生型MET在加工和二聚化方面的基本特性，并以肝细胞生长因子（HGF）依赖性和非依赖性方式增强磷酸化。我们的研究结果表明，ZM通过MET癌蛋白的表达升高和磷酸化诱导胶质瘤。