Malignant glioma is the most common primary brain tumours. It arises from transformed glial cells such as oligodendrocytes precursors or differentiated astrocytes. Due to its ability to broadly infiltrate the brain parenchyma it remains resistant to current therapy and thus bears a very bad prognosis. My PhD project aims at studying the molecular mechanisms involved in glioma invasivity. Transcriptomic analysis of 130 gliomas revealed a sharp decrease in adherens-junction's molecules expression in the most aggressive tumours, the glioblastoma. This alteration of adherens junction proteins in normal and transformed astrocytes is sufficient to increase migration speed and cell propagation in 3D experiments. I then investigated on how the adherens junctions perturbation could affect collective cell migration and found that p120ctn, the major regulator of cadherin stability; is involved in the control of N-cadherin trafficking through its phosphorylation status. Indeed, p120ctn spatially regulates N-cadherin polarized recycling during collective cell migration and its alteration leads to increased astrocyte and glioma cell migration. More precisely, p120ctn, the major regulator of adherens junction stability, was shown to be inversely correlated to the invasive capacity of glioma. A systematic study of p120ctn expression level in a bigger group of patients carefully supervised for their tumor progression is on the way and hopefully will show that p120ctn is a reliable invasivity marker for glioma.
