Mechanisms of malignancy in glioblastoma cells are linked to mitochondrial Ca2 + uniporter upregulation and higher intracellular Ca2+ levels.
Xiaoyun LiRenza SpelatAnna BartoliniDaniela CesselliTamara IusMiran SkrapFederica CaponnettoIvana ManiniYili YangVincent TorrePublished in: Journal of cell science (2020)
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.
Keyphrases
- induced apoptosis
- cell proliferation
- cell cycle arrest
- cell death
- protein kinase
- oxidative stress
- signaling pathway
- poor prognosis
- transcription factor
- squamous cell carcinoma
- endothelial cells
- mass spectrometry
- reactive oxygen species
- pi k akt
- brain injury
- blood brain barrier
- high frequency
- multiple sclerosis
- papillary thyroid
- long non coding rna
- functional connectivity
- transcranial magnetic stimulation
- induced pluripotent stem cells