SP 3

Systems biology of the Unfolded Protein Response in Glioma (SUPR-G)

The unfolded protein response (UPR) is a protective mechanism of the cell, coupled to the endoplasmic reticulum (ER), that is deregulated in many diseases. Especially in glial tumours, which make up 82% of the largest group of malignant tumours of the central nervous system, the UPR can have a negative impact on the successful outcome of treatment. Treatment resistance may develop leading to an undesirable survival of abnormal cells. A basic understanding of the signalling pathways involved, and their cell-stress induced reprogramming, is needed to determine the underlying pathogenetic mechanisms of this effect, and to enable an improved treatment of patients.

Although genome-wide genomic, epigenomic and transcriptional profiles improved the understanding of metabolic changes and molecular aberrations in glioma, the resulting impact on ER Stress and the mechanism driving cell fate decisions via the UPR remain unresolved. Therefore, our objectives are to:

  • construct an UPR and ER Stress interaction network

  • compare the therapeutic response pathways, and

  • predict the UPR system behavior to identify targets which modulate migration and invasion characteristics of glioma cells

bioinformatic, network, integration, protein, interaction

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