Glioma Proteome explored by LC/MS/MS

Gliomas are the most frequent and aggressive malignancies of the central nervous system. Gliomas accumulate genetic alterations that cilminate in enhanced activity of receptor tyrosine kinasesand downstream mediators. The genetic alterations (gene amplification/loss) are well characterised, little information is available regarding the changes in the proteome of gliomas of different grades. Therefore, an unbiased quantitative proteomics approach of human gliomas has been undertaken. The proteomics results indicate various up- and downregulation of pathways, in particular downregulation of the endocytic machinery components involved in initiation, formation, and scission of endocytic carriers. Both clathrin-dependent and -independent endocytosis were changed. The reduction of endocytic machinery components causes increased receptor cell surface levels, a prominent phenotype of defective endocytosis. The impaired endocytosis creates a selective advantage in glioma tumour progression due to prolonged receptor tyrosine signalling from the cell surface.