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

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.

SUBMITTER: Aulestia FJ 

PROVIDER: S-EPMC6021377 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature