Mechanisms of malignancy in glioblastoma cells are linked to mitochondrial Ca uniporter upregulation and higher intracellular Ca levels.

Glioblastoma (GBM) is one of the most malignant brain tumours and, despite advances in treatment modalities, it remains largely incurable. Ca regulation and dynamics play crucial roles in different aspects of cancer, but they have never been investigated in detail in GBM. Here, we report that spontaneous Ca waves in GBM cells cause unusual intracellular Ca ([Ca]) elevations (>1 μM), often propagating through tumour microtubes (TMs) connecting adjacent cells. This unusual [Ca] elevation is not associated with the induction of cell death and is concomitant with overexpression of mitochondrial Ca uniporter (MCU). We show that silencing decreases proliferation and alters [Ca] dynamics in U87 GBM cells, while overexpression increases [Ca] elevation in human astrocytes (HAs). These results suggest that changes in the expression level of MCU, a protein involved in intracellular Ca regulation, influences GBM cell proliferation, contributing to GBM malignancy.This article has an associated First Person interview with the first author of the paper.