Store-Operated Calcium Channels Control Proliferation and Self-Renewal of Cancer Stem Cells from Glioblastoma.
Elodie TerriéNadine DéliotYassine BenzidaneThomas HarnoisLaëtitia CousinPatrick BoisLisa OliverPatricia ArnaultFrançois ValletteBruno ConstantinValérie CoronasPublished in: Cancers (2021)
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.
Keyphrases
- stem cells
- induced apoptosis
- end stage renal disease
- poor prognosis
- squamous cell carcinoma
- chronic kidney disease
- cell proliferation
- young adults
- free survival
- cell therapy
- long non coding rna
- newly diagnosed
- patient reported outcomes
- replacement therapy
- photodynamic therapy
- high resolution
- machine learning
- inflammatory response
- deep learning
- angiotensin ii
- transcription factor
- mass spectrometry
- bone marrow
- nuclear factor
- squamous cell