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Mechanisms of malignancy in glioblastoma cells are linked to mitochondrial Ca2+ uniporter upregulation and higher intracellular Ca2+ levels.

Journal of cell science (2020-02-14)
Xiaoyun Li, Renza Spelat, Anna Bartolini, Daniela Cesselli, Tamara Ius, Miran Skrap, Federica Caponnetto, Ivana Manini, Yili Yang, Vincent Torre
ABSTRACT

Glioblastoma (GBM) is one of the most malignant brain tumours and, despite advances in treatment modalities, it remains largely incurable. Ca2+ 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 Ca2+ waves in GBM cells cause unusual intracellular Ca2+ ([Ca2+]i) elevations (>1 μM), often propagating through tumour microtubes (TMs) connecting adjacent cells. This unusual [Ca2+]i elevation is not associated with the induction of cell death and is concomitant with overexpression of mitochondrial Ca2+ uniporter (MCU). We show that MCU silencing decreases proliferation and alters [Ca2+]i dynamics in U87 GBM cells, while MCU overexpression increases [Ca2+]i elevation in human astrocytes (HAs). These results suggest that changes in the expression level of MCU, a protein involved in intracellular Ca2+ regulation, influences GBM cell proliferation, contributing to GBM malignancy.This article has an associated First Person interview with the first author of the paper.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
青链霉素, Solution stabilized, with 10,000 units penicillin and 10 mg streptomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture
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L -谷氨酰胺 溶液, 200 mM, solution, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
胰岛素 人, recombinant, expressed in yeast (proprietary host)
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抗-MCU 兔抗, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution