Glioblastoma multiforme (GBM) is the most aggressive and frequent brain cancer with a very poor prognosis. It is a highly invasive and infiltrating tumour with glioblastoma cells often invading the normal brain parenchyma. GBM is characterised by an increase in the density and stiffness of the extracellular matrix which contributes to the malignancy of the tumour. GBM cells are shown to spread and migrate faster on substrate with a high rigidity, suggesting that mechanical cues can play a role in the aggressiveness of this tumour. The intermediate filament (IF) vimentin is considered among one of the most common markers of GBM malignancy. Vimentin expression is often associated with an increased invasive potential of cancer cells by promoting cell migration. Our preliminary results have shown that vimentin knockout cells have a strong reduction in chromatin acetylation, a marker that is universally associated with gene transcription. Whether vimentin is involved in the expression of genes involved in the mechanoresponse of GBM still remains unknown. Here we propose to use a multidisciplinary approach combining biophysical techniques with transcriptomic analysis to elucidate the contribution of IFs in the transcriptional regulation of GBM cells undergoing mechanical stress.
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