Acid-sensing ion channel 3 is a new potential therapeutic target for the control of glioblastoma cancer stem cells growth.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Glioblastoma*/metabolism ; Glioblastoma*/pathology ; Glioblastoma*/drug therapy ; Acid Sensing Ion Channels*/metabolism ; Acid Sensing Ion Channels*/genetics ; Neoplastic Stem Cells*/metabolism ; Neoplastic Stem Cells*/drug effects ; Neoplastic Stem Cells*/pathology ; Cell Proliferation*/drug effects ; Brain Neoplasms*/metabolism ; Brain Neoplasms*/pathology ; Brain Neoplasms*/drug therapy; Humans ; Cell Line, Tumor ; Cell Movement/drug effects

Glioblastoma (GBM) is the most common malignant primary brain cancer that, despite recent advances in the understanding of its pathogenesis, remains incurable. GBM contains a subpopulation of cells with stem cell-like properties called cancer stem cells (CSCs). Several studies have demonstrated that CSCs are resistant to conventional chemotherapy and radiation thus representing important targets for novel anti-cancer therapies. Proton sensing receptors expressed by CSCs could represent important factors involved in the adaptation of tumours to the extracellular environment. Accordingly, the expression of acid-sensing ion channels (ASICs), proton-gated sodium channels mainly expressed in the neurons of peripheral (PNS) and central nervous system (CNS), has been demonstrated in several tumours and linked to an increase in cell migration and proliferation. In this paper we report that the ASIC3 isoform, usually absent in the CNS and present in the PNS, is enriched in human GBM CSCs while poorly expressed in the healthy human brain. We propose here a novel therapeutic strategy based on the pharmacological activation of ASIC3, which induces a significant GBM CSCs damage while being non-toxic for neurons. This approach might offer a promising and appealing new translational pathway for the treatment of glioblastoma.
(© 2024. The Author(s).)

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0 (Acid Sensing Ion Channels)
0 (ASIC3 protein, human)

Date Created: 20240903 Date Completed: 20240904 Latest Revision: 20241011

20241011

PMC11372124

10.1038/s41598-024-71623-9

39227705