2. Academic Validation
  3. ERO1a fosters glioblastoma aggressiveness and metabolic flexibility by regulating mitochondria-associated membrane dynamics

ERO1a fosters glioblastoma aggressiveness and metabolic flexibility by regulating mitochondria-associated membrane dynamics

  • Nat Cell Biol. 2026 Jun 12. doi: 10.1038/s41556-026-01980-2.
Arthur Bassot 1,  Lola Violy # 2,  Lucas Gorka # 2,  Lavinia Cigalotto # 3,  Balasubramaniam Namasivayam 2 4,  Ivan Mikaelian 2,  Emma St Johnston 2,  Chao Han 5 6,  Rudy Gadet 2,  Beatrice Alpha-Bazin 7,  Laurine Moindrot 2,  Emilie Clement 2,  Helena Dragic 2,  Marine Crépin 8 9,  Olivier Berdeaux 8 9,  Christophe Vanbelle 10,  Mélina Gautier 10,  Alice Cariou 2,  Louis Larrouquere 2,  Chunmei Wei 2,  Thomas Gudermann 5,  Jann N Sarkaria 11,  Ester Zito 12 13,  Pierre-Yves Dietrich 14,  Paul R Walker 14 15,  Ivan Nemazanyy 16,  Hubert Lincet 2,  Jean Armengaud 7,  Jennifer Rieusset 17,  Paul S Mischel 18,  Elmina Mammadova-Bach 5 6,  Thomas Simmen 19,  Denis Martinvalet 3,  Marie Castets 4,  Erika Cosset 20
Affiliations

Affiliations

  • 1 Department of CITI, Team GLIMMER of Light, Cancer Research Centre of Lyon - CRCL, INSERM U1052, CNRS UMR 5286, Institut Convergence Plascan, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France. [email protected].
  • 2 Department of CITI, Team GLIMMER of Light, Cancer Research Centre of Lyon - CRCL, INSERM U1052, CNRS UMR 5286, Institut Convergence Plascan, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France.
  • 3 Department of Biomedical Sciences, University of Padua, Padova, Italy.
  • 4 Department of CITI, Team Cell Death and Childhood Cancers, Labex DevWeCan, SouthRock Excellence Center, Cancer Research Centre of Lyon - CRCL, INSERM U1052, CNRS UMR 5286, Lyon, France.
  • 5 Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilians University, Munich, Germany.
  • 6 Division of Nephrology, Department of Medicine IV, Ludwig Maximilians University Hospital, Munich, Germany.
  • 7 Département Médicaments et Technologies pour la Santé (DMTS), Université Paris-Saclay, CEA, INRAE, Bagnols-sur-Cèze, France.
  • 8 Institut Agro, Université Bourgogne Europe, CNRS, INRAE, UMR CSGA, Dijon, France.
  • 9 CNRS, INRAE, PROBE Research Infrastructure, ChemoSens facility, Dijon, France.
  • 10 Cell Imaging Platform, Cancer Research Centre of Lyon - CRCL, INSERM U1052, CNRS UMR 5286, Institut Convergence Plascan, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France.
  • 11 Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
  • 12 Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
  • 13 Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
  • 14 Center for Translational Research in Onco-Hematology, Department of Oncology, University Hospital of Geneva, University of Geneva, Swiss Cancer Center Leman (SCCL), Agora Cancer Research Center, Geneva, Switzerland.
  • 15 Laboratory of Immunobiology of Brain Tumors, Center for Translational Research in OncoHematology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
  • 16 Inserm US24, CNRS UAR 3633, SFR Necker, Platform for Metabolic Analyses, Paris, France.
  • 17 CarMeN Laboratory, Université Claude Bernard Lyon 1, INSERM U1060, INRAE U1397, Pierre Benite, France.
  • 18 Department of Pathology and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • 19 Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
  • 20 Department of CITI, Team GLIMMER of Light, Cancer Research Centre of Lyon - CRCL, INSERM U1052, CNRS UMR 5286, Institut Convergence Plascan, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France. [email protected].
  • # Contributed equally.
PMID: 42286227 DOI: 10.1038/s41556-026-01980-2
Abstract

Despite the wealth of data generated in the omics era to investigate molecular drivers, glioblastoma (GBM) remains one of the most incurable cancers with a poor median of survival. Here we unravelled the dynamic crosstalk between the endoplasmic reticulum and mitochondria, known as mitochondria-associated membranes (MAMs) and define how modulation of calcium fluxes and MAM structure influences GBM cell plasticity and metabolic flexibility. We identified ERO1α, whose expression is significantly associated with poor GBM patient survival, as a critical MAM protein that regulates MAM structure, dynamics and calcium-mediated functions. Our data demonstrate that ERO1α activity and expression promotes GBM aggressiveness in vitro and in vivo and enhances mitochondrial Oxidative Phosphorylation. By establishing a direct link between ERO1α-mediated MAM modulation and the antitumour effects of ERO1α inhibition, this work highlights a context-dependent, druggable vulnerability that can be exploited for GBM therapy.

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