Cell-to-cell communication mediates glioblastoma progression in Drosophila.

摘要: Glioblastoma (GB) is the most aggressive and lethal tumour of central nervous system (CNS). GB cells grow rapidly display a network projections (ultra-long microtubes (TMs)), that mediate cell to communication. GB-TMs infiltrate throughout brain, enwrap neurons facilitate depletion signalling molecule wingless (Wg)/WNT from neighbouring healthy neurons. establish positive feedback loop including Wg upregulation activates cJun N-terminal kinase (JNK) pathway matrix metalloproteases (MMPs) production, which in turn promote further TMs infiltration, progression neurodegeneration. Thus, cellular molecular signals other than primary mutations emerge as players GB. Using Drosophila model GB, we describe temporal organization main events occur interactions, neurodegeneration expansion. We define progressive activation JNK mediated by receptor Grindelwald (Grnd) activated ligand Eiger (Egr)/TNFα produced surrounding brain tissue. propose interactions with tissue precede TM expansion conclude non-autonomous progression. These results contribute deciphering complexity versatility these incurable tumours.