WNT vampirization by glioblastoma leads to tumor growth and neurodegeneration
journal contributionposted on 2021-01-18, 02:15 authored by Marta Portela-EstebanMarta Portela-Esteban, Varun Venkataramani, Natasha Fahey-Lozano, Esther Seco, Maria Losada-Perez, Frank Winkler, Sergio Casas-Tintó
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.