Glioblastoma cells vampirize WNT from neurons and trigger a JNK/MMP signaling loop that enhances glioblastoma progression and neurodegeneration

摘要: Glioblastoma (GB) is the most lethal brain tumor, and Wingless (Wg)-related integration site (WNT) pathway activation in these tumors associated with a poor prognosis. Clinically, disease characterized by progressive neurological deficits. However, whether symptoms result from direct or indirect damage to neurons still unresolved. Using Drosophila primary xenografts as models of human GB, we describe, here, mechanism that leads WNT signaling (Wg Drosophila) tumor cells. GB cells display network microtubes (TMs) enwrap neurons, accumulate Wg receptor Frizzled1 (Fz1), and, thereby, deplete causing neurodegeneration. We have defined this process "vampirization." Furthermore, establish positive feedback loop promote their expansion, which activates cJun N-terminal kinase (JNK) cells, turn, JNK post-transcriptional up-regulation accumulation matrix metalloproteinases (MMPs), facilitate TMs' infiltration throughout brain, further depletion neurons. Consequently, proliferate because target, β-catenin, degenerate extinction. Our findings reveal molecular for TM production, infiltration, maintenance can explain both neuron-dependent progression also neural decay GB.