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.

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

Santoni, Giorgio
Primo
;
Amantini, Consuelo
Ultimo
2019-01-01

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.
2019
262
File in questo prodotto:
File Dimensione Formato  
Cancers 2019, vol. 11, art 322.pdf

accesso aperto

Tipologia: Versione Editoriale
Licenza: PUBBLICO - Creative Commons
Dimensione 1.69 MB
Formato Adobe PDF
1.69 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/472944
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 18
social impact