Quiescence status of glioblastoma stem-like cells involves remodelling of Ca2+ signalling and mitochondrial shape

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Abstract

Quiescence is a reversible cell-cycle arrest which allows cancer stem-like cells to evade killing following therapies. Here, we show that proliferating glioblastoma stem-like cells (GSLCs) can be induced and maintained in a quiescent state by lowering the extracellular pH. Through RNAseq analysis we identified Ca2+ signalling genes differentially expressed between proliferating and quiescent GSLCs. Using the bioluminescent Ca2+ reporter EGFP-aequorin we observed that the changes in Ca2+ homeostasis occurring during the switch from proliferation to quiescence are controlled through store-operated channels (SOC) since inhibition of SOC drives proliferating GSLCs to quiescence. We showed that this switch is characterized by an increased capacity of GSLCs' mitochondria to capture Ca2+ and by a dramatic and reversible change of mitochondrial morphology from a tubular to a donut shape. Our data suggest that the remodelling of the Ca2+ homeostasis and the reshaping of mitochondria might favours quiescent GSLCs' survival and their aggressiveness in glioblastoma.

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Aulestia, F. J., Néant, I., Dong, J., Haiech, J., Kilhoffer, M. C., Moreau, M., & Leclerc, C. (2018). Quiescence status of glioblastoma stem-like cells involves remodelling of Ca2+ signalling and mitochondrial shape. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-28157-8

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