Store-Operated Calcium Channels Control Proliferation and Self-Renewal of Cancer Stem Cells from Glioblastoma

Cancers

Nadine Déliot¹  Patricia Arnault¹  Bruno Constantin¹  Laëtitia Cousin¹  Thomas Harnois¹  Yassine Benzidane¹  Valérie Coronas¹  Elodie Terrié¹  Lisa Oliver²  François Vallette²  Patrick Bois³ 

[1] CNRS ERL 7003, Signalisation et Transports Ioniques Membranaires, University of Poitiers, CEDEX 09, 86073 Poitiers, France;CRCINA-UMR 1232 INSERM, Université de Nantes, CEDEX 01, 44007 Nantes, France;EA 4379, Signalisation et Transports Ioniques Membranaires, University of Poitiers, CEDEX 09, 86073 Poitiers, France;

关键词: glioblastoma;    glioma;    cancer stem cell;    calcium channel;    store-operated channel;    TRPC;   

DOI  :  10.3390/cancers13143428

来源: DOAJ

【 摘 要 】

Glioblastoma is the most frequent and deadly form of primary brain tumors. Despite multimodal treatment, more than 90% of patients experience tumor recurrence. Glioblastoma contains a small population of cells, called glioblastoma stem cells (GSC) that are highly resistant to treatment and endowed with the ability to regenerate the tumor, which accounts for tumor recurrence. Transcriptomic studies disclosed an enrichment of calcium (Ca²⁺) signaling transcripts in GSC. In non-excitable cells, store-operated channels (SOC) represent a major route of Ca²⁺ influx. As SOC regulate the self-renewal of adult neural stem cells that are possible cells of origin of GSC, we analyzed the roles of SOC in cultures of GSC previously derived from five different glioblastoma surgical specimens. Immunoblotting and immunocytochemistry experiments showed that GSC express Orai1 and TRPC1, two core SOC proteins, along with their activator STIM1. Ca²⁺ imaging demonstrated that SOC support Ca²⁺ entries in GSC. Pharmacological inhibition of SOC-dependent Ca²⁺ entries decreased proliferation, impaired self-renewal, and reduced expression of the stem cell marker SOX2 in GSC. Our data showing the ability of SOC inhibitors to impede GSC self-renewal paves the way for a strategy to target the cells considered responsible for conveying resistance to treatment and tumor relapse.

【 授权许可】

Unknown