Mechanisms of malignancy in glioblastoma cells are linked to mitochondrial Ca 2 + uniporter upregulation and higher intracellular Ca 2+ levels.

Glioblastoma (GBM) is one of the most malignant brain tumours and, despite advances in treatment modalities, it remains largely incurable. Ca ²⁺ 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 ²⁺ waves in GBM cells cause unusual intracellular Ca ²⁺ ([Ca ²⁺ ] _i ) elevations (>1 μM), often propagating through tumour microtubes (TMs) connecting adjacent cells. This unusual [Ca ²⁺ ] _i elevation is not associated with the induction of cell death and is concomitant with overexpression of mitochondrial Ca ²⁺ uniporter (MCU). We show that MCU silencing decreases proliferation and alters [Ca ²⁺ ] _i dynamics in U87 GBM cells, while MCU overexpression increases [Ca ²⁺ ] _i elevation in human astrocytes (HAs). These results suggest that changes in the expression level of MCU, a protein involved in intracellular Ca ²⁺ regulation, influences GBM cell proliferation, contributing to GBM malignancy.This article has an associated First Person interview with the first author of the paper.
Competing Interests: Competing interestsThe authors declare no competing or financial interests.
(© 2020. Published by The Company of Biologists Ltd.)