Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration

摘要: Glial cells display a network of projections (cytonemes) which mediate cell to communication. Under pathological conditions like glioblastoma (GB), cytonemes transform into ultra-long tumour microtubes (TMs). These filopodia infiltrate through the brain, enwrap neurons and deplete wingless (Wg)/WNT, as consequence GB progress undergo synapse loss degeneration. Thus TMs emerge central cellular feature correlates with poor prognosis in patients animal models. Here we describe Drosophila model for molecular mechanisms behind production, infiltration maintenance. are initially transformed malignant upon EGFR PI3K pathways constitutive activation, afterwards establish positive feedback loop including Wg signalling, JNK matrix metalloproteases (MMP). In order, Frizzled1 mediates signalling upregulation activates GB. As consequence, MMPs upregulated facilitate hence expands further depletion close loop.