Lysosomes in glioblastoma: pump up the volume

Lysosomes are acidic, dynamic organelles that supervise catabolism, integrate signaling cascades, and tune cellular trafficking. Moreover, the loss of their integrity may jeopardize cell viability. In cancer cells, lysosomes are qualitatively and quantitatively modified for the tumor's own benefit. For all these reasons, these organelles emerge as appealing intracellular targets to manipulate non-oncogene addiction. This is of particular interest for brain diseases, including neurodegenerative disorders and cancer, in which stem cells are exhausted and transformed, respectively. Recent publications had demonstrated that stem cells displayed disarmed lysosomes in terms of number and functions during aging and oncogenic progression. Likewise, our laboratory identified that the arginine protease MALT1, normally dedicated to the assembly of proper NF-kB activation and processing a number of substrates, arbitrates lysosome biogenesis and mTOR signaling in glioblastoma stem-like cells. Indeed, blocking either the expression or the activity of this enzyme leads to an aberrant increase of lysosomes, alongside of the down-regulation of the mTOR signaling. This surge of lysosomes eradicates glioblastoma stem-like cells. Targeting lysosomes might thus inspire the design of new strategies to face this devastating human cancer. Here, we provide an overview of the functions of the lysosome as well as its role as a cell death initiator, to highlight the potential of lysosomal drugs for glioblastoma therapy.

Keywords: Lysosome; MALT1; glioma; mTOR; membrane permeabilization; stem cells.