Faraway, so close! Modelling brain cancer in Drosophila

Despite the obvious differences between humans and flies, the analogies of their nervous systems make Drosophila melanogaster an excellent organism in which to model human brain cancers. Glioblastoma multiforme (GBM) is the most common and incurable brain cancer of the adult. It is characterised by a subset of undifferentiated and highly tumourigenic cells, called GBM stem cells (GSC), responsible for malignancy and relapses. Inactivation of the tumour suppressor gene (TSG) PTEN is frequent in primary GBM, resulting in the inhibition of a second TSG, the polarity determinant lgl, due to an ectopic activity of aPKC. Deregulation of this molecular axis is sufficient to reprogramme human neural progenitors into GSC. First, we have proved that the PTEN/aPKC/Lgl axis is conserved also in Drosophila. Second, we have disrupted this conserved axis in type II neuroblasts, a cell population with a lineage similar to that of the mammalian neural stem cells. We obtained a model of invasive tumour that persists and keeps growing in the adult, leading the animals to premature death. This neurogenic model recapitulates many traits typical of human brain cancers, and may help obtain more information on GBM origin, which has long being discussed.