Abstract
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.
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