Post-translational modifications in glioblastoma cells

• Applicant: Privatdozent Dr. Maximilian Scheer
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550676608

Almost all tumour cells show a change in metabolism in the sense of aerobic glycolysis. This phenomenon is also known as the Warburg effect and leads to an accumulation of highly reactive by-products of glycolysis, such as methylglyoxal (MGO). MGO, in turn, is considered one of the most potent precursors for glycation. The modification of metabolic processes also leads to a change in glycosylation on the cell surface. Both of these processes are considered "hallmarks of cancer". Both glycation and glycosylation are post-translational modifications. While these processes have been well researched in other tumour diseases and reaction products, for example, have been established as tumour markers, this has not yet been sufficiently researched in tumours of the nervous system. Preliminary work has shown the influence of MGO on various tumours of the nervous system. In the model used, which utilised meningioma, neuroblastoma and glioblastoma cells, a concentration-dependent effect was observed with regard to both cell viability and the induction of glycation. In addition, an increase in invasiveness was observed in all cell models. These observations correlated with an altered expression of extracellular matrix proteins, such as an increased expression of E-cadherin. In addition to non-enzymatic glycation, the enzymatic process of glycosylation was also modified by MGO and increased polysialylation was detected on the tumour cells. In the analysis of the sialyltransferases, these showed increased expression, which correlated with increased invasiveness. This application will now be used to characterise primary glioma cells with regard to glycation and glycosylation and subsequently modify these processes.

• DFG Programme: Research Grants