Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase - Archive ouverte HAL Access content directly
Journal Articles Cell Death and Disease Year : 2022

Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase

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Joris Guyon
Thierry Virolle
Christophe Antoniewski

Abstract

Abstract Cell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients’ glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients’ tumors isolated cells with high motile potential and highlighted their metabolic specificities. These cells were characterized by enhanced mitochondrial load and oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). Functional assays with patients’ tumor-derived cells and -tissue organoids, and genetic and pharmacological manipulations confirmed that the cells depend on enhanced ROS production and MPST activity for their motility. MPST action involved protection of protein cysteine residues from damaging hyperoxidation. Its knockdown translated in reduced tumor burden, and a robust increase in mice survival. Starting from cell-by-cell analyses of the patients’ tumors, our work unravels metabolic dependencies of cell malignancy maintained across heterogeneous genomic landscapes.
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Origin : Publication funded by an institution

Dates and versions

hal-03836497 , version 1 (04-11-2022)

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Cite

Mirca S Saurty-Seerunghen, Thomas Daubon, Léa Bellenger, Virgile Delaunay, Gloria Castro, et al.. Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase. Cell Death and Disease, 2022, 13 (10), pp.913. ⟨10.1038/s41419-022-05358-8⟩. ⟨hal-03836497⟩
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