Abstract
Recently, the finding of cancer stem cells in brain tumors has increased the possibilities for advancing new therapeutic approaches with the aim to overcome the limits of current available treatments. In addition, a role for ion channels, particularly of TRP channels, in developing neurons as well as in brain cancer development and progression have been demonstrated. Herein, we focus on the latest advancements in understanding the role of TRPV2, a Ca2+ permeable channel belonging to the TRPV subfamily in neurogenesis and gliomagenesis. TRPV2 has been found to be expressed in both neural progenitor cells and glioblastoma stem/progenitor-like cells (GSCs). In developing neurons, post-translational modifications of TRPV2 (e.g., phosphorylation by ERK2) are required to stimulate Ca2+ signaling and nerve growth factor-mediated neurite outgrowth. TRPV2 overexpression also promotes GSC differentiation and reduces gliomagenesis in vitro and in vivo. In glioblastoma, TRPV2 inhibits survival and proliferation, and induces Fas/CD95-dependent apoptosis. Furthermore, by proteomic analysis, the identification of a TRPV2 interactome-based signature and its relation to glioblastoma progression/recurrence, high or low overall survival and drug resistance strongly suggest an important role of the TRPV2 channel as a potential biomarker in glioblastoma prognosis and therapy.
Highlights
The finding of cancer stem cells in brain tumors has increased the possibilities for advancing new therapeutic approaches with the aim to overcome the limits of current available treatments
The recent data collected in this review indicate that the overcoming of chemoresistance in glioblastoma multiforme (GBM) patients could be obtained by treatment with cannabinoids
The expression of the TRPV2 interactome is significantly associated with the reduced survival of GBM patients
Summary
The Transient Receptor Potential Vanilloid (TRPV) subfamily (vanilloid receptors) includes ion channels involved in nociception and thermosensation (from TRPV1 to TRPV4), and in renal Ca2+. The autophagic pathway, stimulated by CBD/TRPV2, reduces cell viability, inhibits the proliferation rate, and causes cell cycle arrest in the G0/G1 phase All these changes have been associated with a marked increase in GFAP and βIII-tubulin expression and a reduction in stem cell marker levels such as CD133, Oct-4, SSEA-1, and nestin, leading to GSC differentiation [14]. Among transcriptional factors regulating neuronal differentiation, Runx, a Runt domain transcription factor known in mammals as AML1 (acute myeloid leukemia 1), has been demonstrated to play a major role It is expressed in embryonic neural tissues and participates in mammalian neurogenesis, in the development of motor and sensory neurons (Figure 4) [45]. The understanding of the molecular mechanisms regulating self-renewal, proliferation, and differentiation of GSCs and the contribution of the different AML-1/Runx isoforms will improve the development of novel therapeutic strategies
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