WNT vampirization by glioblastoma leads to tumor growth and neurodegeneration

SummaryGlioblastoma (GB) is the most lethal brain tumor due to its high proliferation, aggressiveness, infiltration capacity and resilience to current treatments. Activation of the Wingless-related-integration-site (WNT) pathway is associated with a bad prognosis. Using Drosophila and primary xenograft models of human GB, we describe a mechanism that leads to the activation of WNT signaling [Wingless (Wg) in Drosophila] in tumor cells. GB cells display a network of tumor microtubes (TMs) which enwraps neurons, accumulates Wg receptor Frizzled1 (Fz1), and, thereby, actively depletes Wg from the neurons. Consequently, GB cells proliferate due to β-catenin activation, and neurons degenerate due to Wg signaling extinction. This novel view explains both neuron-dependent tumor progression, and also the neural decay associated with GB.