Unravelling the role of doryphagy in Medulloblastoma Cancer Stem Cells

The centriolar satellites (CSs) are highly characterized in the organization of microtubules, but little is known about their degradation and recycling process, particularly in a tumoral environment, such as Medulloblastoma (MB). “Doryphagy” has been recently established as the novel selective form of autophagy for CSs, through the specific binding of Pericentriolar Material 1 (PCM1), as well as other CSs proteins, to the GABARAPs autophagy receptors. In silico analysis of Medulloblastoma (MB) patients’ samples revealed that PCM1 mRNA expression is lowered, as compared to their healthy counterparts, and this correlates with a worse prognosis. CSs are fundamental for correct cell division and Cancer Stem Cells (CSCs) particularly rely on symmetric cell division. Our previous observations state that autophagy can affect stem potential of MB CSCs, and therefore, here we propose to explore the role of doryphagy in this kind of regulation, by shedding light on the possible underlying molecular mechanisms. Indeed, the analyses of several MB cell lines, representing different MB subgroups, revealed that a doryphagy impairment is associated with a negative modulation of the stem potential, both at proliferation and differentiation level, and ultimately leading to cell death. Overall, our results could open a new scenario on the landscape of therapeutic strategies aimed at eradicating CSCs from MBs, paving the way for a novel focused approach.