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Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions
Hui-Min Chen1, Kai Yu2, Xiao-yan Tang2
1Biodynamic 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.
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.
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