2. Academic Validation
  3. Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase

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

  • Cell Death Dis. 2022 Oct 30;13(10):913. doi: 10.1038/s41419-022-05358-8.
Mirca S Saurty-Seerunghen 1,  Thomas Daubon 2,  Léa Bellenger 3,  Virgile Delaunay 1,  Gloria Castro 1,  Joris Guyon 4,  Ahmed Rezk 1,  Sylvie Fabrega 5,  Ahmed Idbaih 6,  Fabien Almairac 7 8,  Fanny Burel-Vandenbos 7 9,  Laurent Turchi 7 10,  Eric Duplus 11,  Thierry Virolle 7,  Jean-Michel Peyrin 12,  Christophe Antoniewski 3,  Hervé Chneiweiss 1,  Elias A El-Habr # 13,  Marie-Pierre Junier # 14
Affiliations

Affiliations

  • 1 CNRS UMR8246, Inserm U1130, Sorbonne Université, Neuroscience Paris Seine-IBPS Laboratory, Team Glial Plasticity and NeuroOncology, Paris, France.
  • 2 CNRS UMR5095, Inserm U1029, Université de Bordeaux, Institut de Biochimie et Génétique Cellulaires, Team Bioenergetics and dynamics of mitochondria, Bordeaux, France.
  • 3 ARTbio Bioinformatics Analysis Facility, Sorbonne Université, CNRS, Institut de Biologie Paris Seine, Paris, France.
  • 4 Inserm U1312, Université de Bordeaux, Pessac, France.
  • 5 Plateforme Vecteurs Viraux et Transfert de Gènes, Université Paris Descartes-Structure Fédérative de Recherche Necker, CNRS UMS3633, Inserm US24, Paris, France.
  • 6 CNRS UMR 7225, Inserm U1127, Sorbonne Université, Institut du Cerveau et de la Moelle épinière, Paris, France.
  • 7 Université Côte D'Azur, CNRS, INSERM, Institut de Biologie Valrose, Team INSERM Cancer Stem Cell Plasticity and Functional Intra-tumor Heterogeneity, Nice, France.
  • 8 Service de Neurochirurgie, Hôpital Pasteur, CHU de Nice, Nice, 06107, France.
  • 9 Service d'anatomopathologie, Hôpital Pasteur, CHU de Nice, Nice, 06107, France.
  • 10 DRCI, CHU de Nice, Nice, 06107, France.
  • 11 CNRS UMR8256, INSERM ERL1164, Sorbonne Université, Biological adaptation and aging-IBPS Laboratory, Team Integrated cellular aging and inflammation, Paris, France.
  • 12 CNRS UMR8246, Inserm U1130, Sorbonne Université, Neuroscience Paris Seine-IBPS Laboratory, Team Axonal degeneration and regeneration, Paris, France.
  • 13 CNRS UMR8246, Inserm U1130, Sorbonne Université, Neuroscience Paris Seine-IBPS Laboratory, Team Glial Plasticity and NeuroOncology, Paris, France. [email protected].
  • 14 CNRS UMR8246, Inserm U1130, Sorbonne Université, Neuroscience Paris Seine-IBPS Laboratory, Team Glial Plasticity and NeuroOncology, Paris, France. [email protected].
  • # Contributed equally.
PMID: 36310164 DOI: 10.1038/s41419-022-05358-8
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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