Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors

AbstractAccumulating data shows that altered metabolic activity contributes to glioma development. Recently, modulation of SSADH (succinic semialdehyde dehydrogenase) expression, implicated in the catabolism of GABA neurotransmitter, was shown to impact glioma cell properties, such as proliferation, self-renewal and tumorigenicity. The purpose of this study was to investigate the clinical significance of SSADH expression in human gliomas.  Using public single-cell RNA-sequencing data from glioma surgical resections, we initially grouped cancer cells according toALDH5A1 (Aldehyde dehydrogenase 5 family member A1) expression, which encodes SSADH. Gene ontology  enrichment analysis of genes differentially expressed between cancer cells expressing high or low levels of ALDH5A1, highlighted enrichment in genes implicated in cell morphogenesis and motility. In glioblastoma cell lines, ALDH5A1 knockdown inhibited cell proliferation, induced apoptosis and red uced their migratory potential. This was accompanied by a reduction in the mRNA levels of the adherens junction moleculeADAM-15 and deregulation in the expression of EMT  biomarkers, with increasedCDH1 and decreasedvimentin mRNA levels. Evaluation of SSADH expression in a cohort of 95 gliomas using immunohistochemistry showed that SSADH expression was significantly elevated in cancer tissues  compared to normal brain tissues, without any significant correlation with clinicopathological characteristics. In summary, our data...
Source: Neurotherapeutics - Category: Neurology Source Type: research