title: ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.
abstract: Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Esen Yonca
authors.identifier: 0000-0001-8870-7040
authors.initials: EY
authors.lastname: Bassoy
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.|Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kasahara
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Valentina
authors.identifier: 0000-0002-5470-8181
authors.initials: V
authors.lastname: Chiusolo
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jacquemin
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Emma
authors.initials: E
authors.lastname: Boydell
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zamorano
authors.affiliation: Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Riccadonna
authors.affiliation: Department of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pellegatta
authors.affiliation: Biomathematical and Biostatistical Analysis, Institute of Genetics and Genomics University of Geneva, Geneva, Switzerland.
authors.forename: Nicolas
authors.identifier: 0000-0003-2640-636X
authors.initials: N
authors.lastname: Hulo
authors.affiliation: Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dutoit
authors.affiliation: Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.|Amal Therapeutics, Geneva, Switzerland.
authors.forename: Madiha
authors.initials: M
authors.lastname: Derouazi
authors.affiliation: Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Dietrich
authors.affiliation: Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Walker
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland denis.martinvalet@unige.ch.
authors.forename: Denis
authors.identifier: 0000-0002-6027-1270
authors.initials: D
authors.lastname: Martinvalet
mesh_terms: D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology*; D011134:Polysaccharides / Q000096:biosynthesis*; D013234:Stem Cells / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D011134:Polysaccharides
keywords: ER–mitochondria contacts; cancer cell glycocalyx; cytotoxic lymphocytes; glioma; glioma stem‐like cells