Comprehensive protein tyrosine phosphatase mRNA profiling identifies new regulators in the progression of glioma

Abstract

The infiltrative behavior of diffuse gliomas severely reduces therapeutic potential of surgical resection and radiotherapy, and urges for the identification of new drug-targets affecting glioma growth and migration. To address the potential role of protein tyrosine phosphatases (PTPs), we performed mRNA expression profiling for 91 of the 109 known human PTP genes on a series of clinical diffuse glioma samples of different grades and compared our findings with in silico knowledge from REMBRANDT and TCGA databases. Overall PTP family expression levels appeared independent of characteristic genetic aberrations associated with lower grade or high grade gliomas. Notably, seven PTP genes (DUSP26, MTMR4, PTEN, PTPRM, PTPRN2, PTPRT and PTPRZ1) were differentially expressed between grade II-III gliomas and (grade IV) glioblastomas. For DUSP26, PTEN, PTPRM and PTPRT, lower expression levels correlated with poor prognosis, and overexpression of DUSP26 or PTPRT in E98 glioblastoma cells reduced tumorigenicity. Our study represents the first in-depth analysis of PTP family expression in diffuse glioma subtypes and warrants further investigations into PTP-dependent signaling events as new entry points for improved therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0372-x) contains supplementary material, which is available to authorized users.

Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases

“…Some years back, we reviewed a list of PTP genes that bear links to gliomagenesis [ 121 ]. More recently, we classified a subset of PTPs as possible entry points for glioma treatment based on a comparison of their relative expression levels in normal and tumor brain material combined with expression and survival data from relevant databases [ 122 ]. Three of these genes ( PTPRZ1 , PTEN , PTPRT ) encode PTPs with C-terminal PDZ binding motifs [ 116 , 123 ] and mapping of the interacting PDZ domain-containing proteins may be of relevance for glioblastoma etiology.…”

“…This may well involve PTPN13. In addition, for the PDZ target sequence (“SSF”; [ 116 ]) in the glioblastoma-relevant PTPRT [ 122 ] knowledge on the glioblastoma PDZ interactome could provide new therapeutic avenues.…”

Haplotype Block Analysis Reveals Candidate Genes and QTLs for Meat Quality and Disease Resistance in Chinese Jiangquhai Pig Breed

“…Intriguingly, among all the Chinese breeds in our study, the JQ breed had the highest number of SNPs in a block, with 80 SNPs in Block 22 of Chromosome 18 (923784 bp – 1002867 bp). This block overlaps the protein tyrosine phosphatase receptor ( PTPRN2 ) gene, which suggests that it is associated with oncogenic processes ( Bourgonje et al, 2016 ). This gene is also predominantly expressed in endocrine and neuronal cells, where it functions in exocytosis ( Sorokin et al, 2015 ).…”

Computational identification and characterization of glioma candidate biomarkers through multi-omics integrative profiling

“…Noticeably, some of these PRKCG-like genes have already been reported to be closely related with glioma [88][89][90][91][92]. For instance, AKAP6 (A-kinase anchoring protein 6) polymorphisms are associated with glioma susceptibility and prognosis [91]; Phosphorylated SATB1 (SATB homeobox 1) contributes to the invasive and proliferative of GBM cells and is associated with glioma prognosis [88]; Higher expression of CDK17 (cyclin dependent kinase 17) is indicative of longer overall survival [89]; PTPRM (protein tyrosine phosphatase receptor type M) expression is significantly reduced in GBM by contrast to LGG and higher expression is indicative of longer overall survival [90]; and CHD5 (chromodomain helicase DNA binding protein 5) might act as a tumor suppressor and its lower expression is associated with poor prognosis in glioma [92]. Among these PRKCG-like genes, we revealed that 114 genes show negative correlations between methylation level and expression level, whereas 297 genes present positive correlations (Additional file 1: Table S3).…”