The Transient Receptor Potential Vanilloid Type-2(TRPV2) Ion Channels in Neurogenesis andGliomagenesis: Cross-Talk between TranscriptionFactors and Signaling Molecules.

Recently, the finding of cancer stem cells in brain tumors has increased the possibilitiesfor advancing new therapeutic approaches with the aim to overcome the limits of current availabletreatments. In addition, a role for ion channels, particularly of TRP channels, in developing neuronsas well as in brain cancer development and progression have been demonstrated. Herein, we focuson the latest advancements in understanding the role of TRPV2, a Ca2+ permeable channel belongingto the TRPV subfamily in neurogenesis and gliomagenesis. TRPV2 has been found to be expressedin both neural progenitor cells and glioblastoma stem/progenitor-like cells (GSCs). In developingneurons, post-translational modifications of TRPV2 (e.g., phosphorylation by ERK2) are required tostimulate Ca2+ signaling and nerve growth factor-mediated neurite outgrowth. TRPV2overexpression also promotes GSC differentiation and reduces gliomagenesis in vitro and in vivo.In glioblastoma, TRPV2 inhibits survival and proliferation, and induces Fas/CD95-dependentapoptosis. Furthermore, by proteomic analysis, the identification of a TRPV2 interactome-basedsignature and its relation to glioblastoma progression/recurrence, high or low overall survival anddrug resistance strongly suggest an important role of the TRPV2 channel as a potential biomarkerin glioblastoma prognosis and therapy.